Enzyme Nomenclature

EC 4.2.3 (continued)

Acting on Phosphates

Continued from EC 4.2.3.1 to EC 4.2.3.50 EC 4.2.3.51 to EC 4.2.3.100 and EC 4.2.3.101 to EC 4.2.3.150.

Contents

EC 4.2.3.151 pentamethylcyclopentadecatrienol synthase
EC 4.2.3.152 2-epi-5-epi-valiolone synthase
EC 4.2.3.153 (5-formylfuran-3-yl)methyl phosphate synthase
EC 4.2.3.154 demethyl-4-deoxygadusol synthase
EC 4.2.3.155 2-epi-valiolone synthase
EC 4.2.3.156 hydroxysqualene synthase
EC 4.2.3.157 (+)-isoafricanol synthase
EC 4.2.3.158 (–)-spiroviolene synthase
EC 4.2.3.159 tsukubadiene synthase
EC 4.2.3.160 (2S,3R,6S,9S)-(–)-protoillud-7-ene synthase
EC 4.2.3.161 (3S)-(+)-asterisca-2(9),6-diene synthase
EC 4.2.3.162 (–)-α-amorphene synthase
EC 4.2.3.163 (+)-corvol ether B synthase
EC 4.2.3.164 (+)-eremophilene synthase
EC 4.2.3.165 (1R,4R,5S)-(–)-guaia-6,10(14)-diene synthase
EC 4.2.3.166 (+)-(1E,4E,6S,7R)-germacra-1(10),4-dien-6-ol synthase
EC 4.2.3.167 dolabella-3,7-dien-18-ol synthase
EC 4.2.3.168 dolathalia-3,7,11-triene synthase
EC 4.2.3.169 7-epi-α-eudesmol synthase
EC 4.2.3.170 4-epi-cubebol synthase
EC 4.2.3.171 (+)-corvol ether A synthase
EC 4.2.3.172 10-epi-juneol synthase
EC 4.2.3.173 τ-cadinol synthase
EC 4.2.3.174 (2E,6E)-hedycaryol synthase
EC 4.2.3.175 10-epi-cubebol synthase
EC 4.2.3.176 sesterfisherol synthase
EC 4.2.3.177 β-thujene synthase
EC 4.2.3.178 stellata-2,6,19-triene synthase
EC 4.2.3.179 guaia-4,6-diene synthase
EC 4.2.3.180 pseudolaratriene synthase
EC 4.2.3.181 selina-4(15),7(11)-diene synthase
EC 4.2.3.182 pristinol synthase
EC 4.2.3.183 nezukol synthase
EC 4.2.3.184 5-hydroxy-α-gurjunene synthase
EC 4.2.3.185 ent-atiserene synthase
EC 4.2.3.186 ent-13-epi-manoyl oxide synthase
EC 4.2.3.187 (2Z,6E)-hedycaryol synthase
EC 4.2.3.188 β-geranylfarnesene synthase
EC 4.2.3.189 9,13-epoxylabda-14-ene synthase
EC 4.2.3.190 manoyl oxide synthase
EC 4.2.3.191 cycloaraneosene synthase
EC 4.2.3.192 labda-7,13(16),14-triene synthase
EC 4.2.3.193 (12E)-labda-8(17),12,14-triene synthase
EC 4.2.3.194 (–)-drimenol synthase
EC 4.2.3.195 rhizathalene A synthase
EC 4.2.3.196 dolabradiene synthase
EC 4.2.3.197 eudesmane-5,11-diol synthase
EC 4.2.3.198 α-selinene synthase
EC 4.2.3.199 (–)-5-epieremophilene synthase
EC 4.2.3.200 β-pinacene synthase

See the following file for:
EC 4.2.3.1 to EC 4.2.3.50, EC 4.2.3.51 to EC 4.2.3.100 and EC 4.2.3.101 to EC 4.2.3.150 .


Entries

EC 4.2.3.101

Accepted name: 7-epi-sesquithujene synthase

Reaction: (2E,6E)-farnesyl diphosphate = 7-epi-sesquithujene + diphosphate

For diagram of reaction click here and mechanism click here.

Other name(s): TPS4-B73

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (7-epi-sesquithujene-forming)

Comments: The enzyme from Zea mays, variety B73, gives mainly 7-epi-sesquithujene with (S)-β-bisabolene and traces of other sesquiterpenoids, cf. EC 4.2.3.55 (S)-β-bisabolene synthase. It requires Mg2+ or Mn2+. The product ratio is dependent on which metal ion is present. 7-epi-Sesquithujene is an attractant for the emerald ash borer beetle.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Köllner, T.G., Schnee, C., Gershenzon, J. and Degenhardt, J. The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes. Plant Cell 16 (2004) 1115-1131. [PMID: 15075399]

[EC 4.2.3.101 created 2012]

EC 4.2.3.102

Accepted name: sesquithujene synthase

Reaction: (2E,6E)-farnesyl diphosphate = sesquithujene + diphosphate

For diagram of reaction click here and mechanism click here.

Other name(s): TPS5-Del1

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (sesquithujene-forming)

Comments: The enzyme from Zea mays, variety Delprim, gives mainly sesquithujene with (S)-β-bisabolene and (E)-β-farnesene plus traces of other sesquiterpenoids, cf. EC 4.2.3.55 [(S)-β-bisabolene synthase] and EC 4.2.3.47 (β-farnesene synthase). It requires Mg2+ or Mn2+. The exact product ratio is dependent on which metal ion is present.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Köllner, T.G., Schnee, C., Gershenzon, J. and Degenhardt, J. The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes. Plant Cell 16 (2004) 1115-1131. [PMID: 15075399]

[EC 4.2.3.102 created 2012]

EC 4.2.3.103

Accepted name: ent-isokaurene synthase

Reaction: ent-copalyl diphosphate = ent-isokaurene + diphosphate

For diagram of reaction click here and mechanism click here.

Other name(s): OsKSL5i; OsKSL6

Systematic name: ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-isokaurene-forming)

Comments: Two enzymes of the rice sub-species Oryza sativa ssp. indica, OsKSL5 and OsKSL6, produce ent-isokaurene. A variant of OsKSL5 from the sub-species Oryza sativa ssp. japonica produces ent-pimara-8(14),15-diene instead [cf. EC 4.2.3.30, ent-pimara-8(14),15-diene synthase].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Xu, M., Wilderman, P.R., Morrone, D., Xu, J., Roy, A., Margis-Pinheiro, M., Upadhyaya, N.M., Coates, R.M. and Peters, R.J. Functional characterization of the rice kaurene synthase-like gene family. Phytochemistry 68 (2007) 312-326. [PMID: 17141283]

2. Xu, M., Wilderman, P.R. and Peters, R.J. Following evolution’s lead to a single residue switch for diterpene synthase product outcome. Proc. Natl. Acad. Sci. USA 104 (2007) 7397-7401. [PMID: 17456599]

[EC 4.2.3.103 created 2012]

EC 4.2.3.104

Accepted name: α-humulene synthase

Reaction: (2E,6E)-farnesyl diphosphate = α-humulene + diphosphate

For diagram of reaction click here.

Other name(s): ZSS1

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-humulene-forming)

Comments: The enzyme from Zingiber zerumbet, shampoo ginger, also gives traces of β-caryophyllene.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Yu, F., Okamto, S., Nakasone, K., Adachi, K., Matsuda, S., Harada, H., Misawa, N. and Utsumi, R. Molecular cloning and functional characterization of α-humulene synthase, a possible key enzyme of zerumbone biosynthesis in shampoo ginger (Zingiber zerumbet Smith). Planta 227 (2008) 1291-1299. [PMID: 18273640]

[EC 4.2.3.104 created 2012]

EC 4.2.3.105

Accepted name: tricyclene synthase

Reaction: geranyl diphosphate = tricyclene + diphosphate

For diagram of reaction click here.

Other name(s): TPS3

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing; tricyclene-forming)

Comments: The enzyme from Solanum lycopersicum (tomato) gives a mixture of tricyclene, camphene, β-myrcene, limonene, and traces of several other monoterpenoids. See EC 4.2.3.117. (–)-camphene synthase, EC 4.2.3.15, myrcene synthase and EC 4.2.3.16, (4S)-limonene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Falara, V., Akhtar, T.A., Nguyen, T.T., Spyropoulou, E.A., Bleeker, P.M., Schauvinhold, I., Matsuba, Y., Bonini, M.E., Schilmiller, A.L., Last, R.L., Schuurink, R.C. and Pichersky, E. The tomato terpene synthase gene family. Plant Physiol. 157 (2011) 770-789. [PMID: 21813655]

[EC 4.2.3.105 created 2012]

EC 4.2.3.106

Accepted name: (E)-β-ocimene synthase

Reaction: geranyl diphosphate = (E)-β-ocimene + diphosphate

For diagram of reaction click here.

Glossary: (E)-β-ocimene = (3E)-3,7-dimethylocta-1,3,6-triene

Other name(s): β-ocimene synthase; AtTPS03; ama0a23; LjEβOS; MtEBOS

Systematic name: geranyl-diphosphate diphosphate-lyase [(E)-β-ocimene-forming]

Comments: Widely distributed in plants, which release β-ocimene when attacked by herbivorous insects.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Faldt, J., Arimura, G., Gershenzon, J., Takabayashi, J. and Bohlmann, J. Functional identification of AtTPS03 as (E)-β-ocimene synthase: a monoterpene synthase catalyzing jasmonate- and wound-induced volatile formation in Arabidopsis thaliana. Planta 216 (2003) 745-751. [PMID: 12624761]

2. Dudareva, N., Martin, D., Kish, C.M., Kolosova, N., Gorenstein, N., Faldt, J., Miller, B. and Bohlmann, J. (E)-β-ocimene and myrcene synthase genes of floral scent biosynthesis in snapdragon: function and expression of three terpene synthase genes of a new terpene synthase subfamily. Plant Cell 15 (2003) 1227-1241. [PMID: 12724546]

3. Arimura, G., Ozawa, R., Kugimiya, S., Takabayashi, J. and Bohlmann, J. Herbivore-induced defense response in a model legume. Two-spotted spider mites induce emission of (E)-β-ocimene and transcript accumulation of (E)-β-ocimene synthase in Lotus japonicus. Plant Physiol. 135 (2004) 1976-1983. [PMID: 15310830]

4. Navia-Gine, W.G., Yuan, J.S., Mauromoustakos, A., Murphy, J.B., Chen, F. and Korth, K.L. Medicago truncatula (E)-β-ocimene synthase is induced by insect herbivory with corresponding increases in emission of volatile ocimene. Plant Physiol. Biochem. 47 (2009) 416-425. [PMID: 19249223]

[EC 4.2.3.106 created 2012]

EC 4.2.3.107

Accepted name: (+)-car-3-ene synthase

Reaction: geranyl diphosphate = (+)-car-3-ene + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: (+)-car-3-ene = (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene

Other name(s): 3-carene cyclase; 3-carene synthase; 3CAR; (+)-3-carene synthase

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-car-3-ene-forming]

Comments: The enzyme reacts with (3S)-linalyl diphosphate twice as rapidly as geranyl diphosphate, but 25 times as rapidly as (3R)-linalyl diphosphate. It is assumed that (3S)-linalyl diphosphate is normally formed as an enzyme bound intermediate in the reaction. In the reaction the 5-pro-R hydrogen of geranyl diphosphate is eliminated during cyclopropane ring formation [1,2]. In Picea abies (Norway spruce) and Picea sitchensis (Sitka spruce) terpinolene is also formed [4,6]. See EC 4.2.3.113 terpinolene synthase. (+)-Car-3-ene is associated with resistance of Picea sitchensis (Sitka spruce) to white pine weevil [6].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Savage, T.J. and Croteau, R. Biosynthesis of monoterpenes: regio- and stereochemistry of (+)-3-carene biosynthesis. Arch. Biochem. Biophys. 305 (1993) 581-587. [PMID: 8373196]

2. Savage, T.J., Ichii, H., Hume, S.D., Little, D.B. and Croteau, R. Monoterpene synthases from gymnosperms and angiosperms: stereospecificity and inactivation by cysteinyl- and arginyl-directed modifying reagents. Arch. Biochem. Biophys. 320 (1995) 257-265. [PMID: 7625832]

3. Savage, T.J., Hatch, M.W. and Croteau, R. Monoterpene synthases of Pinus contorta and related conifers. A new class of terpenoid cyclase. J. Biol. Chem. 269 (1994) 4012-4020. [PMID: 8307957]

4. Faldt, J., Martin, D., Miller, B., Rawat, S. and Bohlmann, J. Traumatic resin defense in Norway spruce (Picea abies): methyl jasmonate-induced terpene synthase gene expression, and cDNA cloning and functional characterization of (+)-3-carene synthase. Plant Mol. Biol. 51 (2003) 119-133. [PMID: 12602896]

5. Hamberger, B., Hall, D., Yuen, M., Oddy, C., Hamberger, B., Keeling, C.I., Ritland, C., Ritland, K. and Bohlmann, J. Targeted isolation, sequence assembly and characterization of two white spruce (Picea glauca) BAC clones for terpenoid synthase and cytochrome P450 genes involved in conifer defence reveal insights into a conifer genome. BMC Plant Biol. 9 (2009) 106. [PMID: 19656416]

6. Hall, D.E., Robert, J.A., Keeling, C.I., Domanski, D., Quesada, A.L., Jancsik, S., Kuzyk, M.A., Hamberger, B., Borchers, C.H. and Bohlmann, J. An integrated genomic, proteomic and biochemical analysis of (+)-3-carene biosynthesis in Sitka spruce (Picea sitchensis) genotypes that are resistant or susceptible to white pine weevil. Plant J. 65 (2011) 936-948. [PMID: 21323772]

[EC 4.2.3.107 created 2012]

EC 4.2.3.108

Accepted name: 1,8-cineole synthase

Reaction: geranyl diphosphate + H2O = 1,8-cineole + diphosphate

For diagram of reaction click here.

Glossary: 1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

Other name(s): 1,8-cineole cyclase; geranyl pyrophoshate:1,8-cineole cyclase; 1,8-cineole synthetase

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, 1,8-cineole-forming)

Comments: Requires Mn2+ or Zn2+. Mg2+ is less effective than either. 1,8-Cineol is the main product from the enzyme with just traces of other monoterpenoids. The oxygen atom is derived from water. The reaction proceeds via linalyl diphosphate and α-terpineol, the stereochemistry of both depends on the organism. However neither intermediate can substitute for geranyl diphosphate. The reaction in Salvia officinalis (sage) proceeds via (–)-(3R)-linalyl diphosphate [1-3] while that in Arabidopsis (rock cress) proceeds via (+)-(3S)-linalyl diphosphate [4].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Croteau, R., Alonso, W.R., Koepp, A.E. and Johnson, M.A. Biosynthesis of monoterpenes: partial purification, characterization, and mechanism of action of 1,8-cineole synthase. Arch. Biochem. Biophys. 309 (1994) 184-192. [PMID: 8117108]

2. Wise, M.L., Savage, T.J., Katahira, E. and Croteau, R. Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase. J. Biol. Chem. 273 (1998) 14891-14899. [PMID: 9614092]

3. Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203-211. [PMID: 12941302]

4. Chen, F., Ro, D.K., Petri, J., Gershenzon, J., Bohlmann, J., Pichersky, E. and Tholl, D. Characterization of a root-specific Arabidopsis terpene synthase responsible for the formation of the volatile monoterpene 1,8-cineole. Plant Physiol. 135 (2004) 1956-1966. [PMID: 15299125]

5. Keszei, A., Brubaker, C.L., Carter, R., Kollner, T., Degenhardt, J. and Foley, W.J. Functional and evolutionary relationships between terpene synthases from Australian Myrtaceae. Phytochemistry 71 (2010) 844-852. [PMID: 20399476]

[EC 4.2.3.108 created 2012]

EC 4.2.3.109

Accepted name: (–)-sabinene synthase

Reaction: geranyl diphosphate = (–)-sabinene + diphosphate

For diagram of reaction click here.

Glossary: (–)-sabinene = (1S,5S)-1-isopropyl-4-methylenebicyclo[3.1.0]hexane

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (–)-sabinene-forming]

Comments: Requires Mg2+. Isolated from Pinus contorta (lodgepole pine) as cyclase I [1] and from Conocephalum conicum (liverwort) [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Savage, T.J., Hatch, M.W. and Croteau, R. Monoterpene synthases of Pinus contorta and related conifers. A new class of terpenoid cyclase. J. Biol. Chem. 269 (1994) 4012-4020. [PMID: 8307957]

2. Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203-211. [PMID: 12941302]

[EC 4.2.3.109 created 2012]

EC 4.2.3.110

Accepted name: (+)-sabinene synthase

Reaction: geranyl diphosphate = (+)-sabinene + diphosphate

For diagram of reaction click here.

Glossary: (+)-sabinene = (+)-thuj-4(10)-ene = (1R,5R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexane

Other name(s): SS

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-sabinene-forming]

Comments: Isolated from Salvia officinalis (sage). The recombinant enzyme gave 63% (+)-sabinene, 21% γ-terpinene, and traces of other monoterpenoids. See EC 4.2.3.114 γ-terpinene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Wise, M.L., Savage, T.J., Katahira, E. and Croteau, R. Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase. J. Biol. Chem. 273 (1998) 14891-14899. [PMID: 9614092]

2. Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203-211. [PMID: 12941302]

[EC 4.2.3.110 created 2012]

EC 4.2.3.111

Accepted name: (–)-α-terpineol synthase

Reaction: geranyl diphosphate + H2O = (–)-α-terpineol + diphosphate

For diagram of reaction click here.

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (–)-α-terpineol-forming]

Comments: The enzyme has been characterized from Vitis vinifera (grape). Also forms some 1,8-cineole and traces of other monoterpenoids.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Martin, D.M. and Bohlmann, J. Identification of Vitis vinifera (–)-α-terpineol synthase by in silico screening of full-length cDNA ESTs and functional characterization of recombinant terpene synthase. Phytochemistry 65 (2004) 1223-1229. [PMID: 15184006]

2. Lucker, J., Bowen, P. and Bohlmann, J. Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene synthase cDNAs encoding (+)-valencene synthase and (–)-germacrene D synthase and expression of mono- and sesquiterpene synthases in grapevine flowers and berries. Phytochemistry 65 (2004) 2649-2659. [PMID: 15464152]

[EC 4.2.3.111 created 2012]

EC 4.2.3.112

Accepted name: (+)-α-terpineol synthase

Reaction: geranyl diphosphate + H2O = (+)-α-terpineol + diphosphate

For diagram of reaction click here.

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-α-terpineol-forming]

Comments: The enzyme has been characterized from Santalum album (sandalwood). Also forms some (–)-limonene and traces of other monoterpenoids. See EC 4.2.3.16 (4S)-limonene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Jones, C.G., Keeling, C.I., Ghisalberti, E.L., Barbour, E.L., Plummer, J.A. and Bohlmann, J. Isolation of cDNAs and functional characterisation of two multi-product terpene synthase enzymes from sandalwood, Santalum album L. Arch. Biochem. Biophys. 477 (2008) 121-130. [PMID: 18541135]

[EC 4.2.3.112 created 2012]

EC 4.2.3.113

Accepted name: terpinolene synthase

Reaction: geranyl diphosphate = terpinolene + diphosphate

For diagram of reaction click here.

Glossary: terpinolene = 1-methyl-4-(propan-2-ylidene)cyclohexene

Other name(s): ag9; PmeTPS2; LaLIMS_RR

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, terpinolene-forming)

Comments: Requires Mg2+. Mn2+ is less effective and product ratio changes. Forms traces of other monoterpenoids.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Croteau, R. and Satterwhite, D.M. Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (–)-pinene cyclases from sage. J. Biol. Chem. 264 (1989) 15309-15315. [PMID: 2768265]

2. Bohlmann, J., Phillips, M., Ramachandiran, V., Katoh, S. and Croteau, R. cDNA cloning, characterization, and functional expression of four new monoterpene synthase members of the Tpsd gene family from grand fir (Abies grandis). Arch. Biochem. Biophys. 368 (1999) 232-243. [PMID: 10441373]

3. Faldt, J., Martin, D., Miller, B., Rawat, S. and Bohlmann, J. Traumatic resin defense in Norway spruce (Picea abies): methyl jasmonate-induced terpene synthase gene expression, and cDNA cloning and functional characterization of (+)-3-carene synthase. Plant Mol. Biol. 51 (2003) 119-133. [PMID: 12602896]

4. Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427-1439. [PMID: 15921711]

5. Landmann, C., Fink, B., Festner, M., Dregus, M., Engel, K.H. and Schwab, W. Cloning and functional characterization of three terpene synthases from lavender (Lavandula angustifolia). Arch. Biochem. Biophys. 465 (2007) 417-429. [PMID: 17662687]

[EC 4.2.3.113 created 2012]

EC 4.2.3.114

Accepted name: γ-terpinene synthase

Reaction: geranyl diphosphate = γ-terpinene + diphosphate

For diagram of reaction click here.

Glossary: γ-terpinene = 1-isopropyl-4-methylcyclohexa-1,4-diene

Other name(s): OvTPS2; ClcTS

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, γ-terpinene-forming)

Comments: Isolated from Thymus vulgaris (thyme) [1,2], Citrus limon (lemon) [3], Citrus unshiu (satsuma) [4} and Origanum vulgare (oregano) [5]. Requires Mg2+. Mn2+ less effective. The reaction involves a 1,2-hydride shift. The 5-pro-S hydrogen of geranyl diphosphate is lost. Traces of several other monoterpenoids are formed in addition to γ-terpinene.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Alonso, W.R. and Croteau, R. Purification and characterization of the monoterpene cyclase γ-terpinene synthase from Thymus vulgaris. Arch. Biochem. Biophys. 286 (1991) 511-517. [PMID: 1897973]

2. LaFever, R.E. and Croteau, R. Hydride shifts in the biosynthesis of the p-menthane monoterpenes α-terpinene, γ-terpinene, and β-phellandrene. Arch. Biochem. Biophys. 301 (1993) 361-366. [PMID: 8460944]

3. Lücker, J., El Tamer, M.K., Schwab, W., Verstappen, F.W., van der Plas, L.H., Bouwmeester, H.J. and Verhoeven, H.A. Monoterpene biosynthesis in lemon (Citrus limon). cDNA isolation and functional analysis of four monoterpene synthases. Eur. J. Biochem. 269 (2000) 3160-3171. [PMID: 12084056]

4. Suzuki, Y., Sakai, H., Shimada, T., Omura, M., Kumazawa, S. and Nakayama, T. Characterization of γ-terpinene synthase from Citrus unshiu (Satsuma mandarin). Biofactors 21 (2004) 79-82. [PMID: 15630174]

5. Crocoll, C., Asbach, J., Novak, J., Gershenzon, J. and Degenhardt, J. Terpene synthases of oregano (Origanum vulgare L.) and their roles in the pathway and regulation of terpene biosynthesis. Plant Mol. Biol. 73 (2010) 587-603. [PMID: 20419468]

[EC 4.2.3.114 created 2012]

EC 4.2.3.115

Accepted name: α-terpinene synthase

Reaction: geranyl diphosphate = α-terpinene + diphosphate

For diagram of reaction click here.

Glossary: α-terpinene = 1-isopropyl-4-methylcyclohexa-1,3-diene

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, α-terpinene-forming)

Comments: The enzyme has been characterized from Dysphania ambrosioides (American wormseed). Requires Mg2+. Mn2+ is less effective. The enzyme will also use (3R)-linalyl diphosphate. The reaction involves a 1,2-hydride shift. The 1-pro-S hydrogen of geranyl diphosphate is lost.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Poulose, A.J. and Croteau, R. γ-Terpinene synthetase: a key enzyme in the biosynthesis of aromatic monoterpenes. Arch. Biochem. Biophys. 191 (1978) 400-411. [PMID: 736574]

2. LaFever, R.E. and Croteau, R. Hydride shifts in the biosynthesis of the p-menthane monoterpenes α-terpinene, γ-terpinene, and β-phellandrene. Arch. Biochem. Biophys. 301 (1993) 361-366. [PMID: 8460944]

[EC 4.2.3.115 created 2012]

EC 4.2.3.116

Accepted name: (+)-camphene synthase

Reaction: geranyl diphosphate = (+)-camphene + diphosphate

For diagram of reaction click here.

Glossary: (+)-camphene = (1R,4S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-camphene-forming]

Comments: Cyclase I of Salvia officinalis (sage) gives about equal parts (+)-camphene and (+)-α-pinene. (3R)-Linalyl diphosphate can also be used by the enzyme in preference to (3S)-linalyl diphosphate. Requires Mg2+ (preferred to Mn2+). See also EC 4.2.3.121 (+)-α-pinene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Gambliel, H. and Croteau, R. Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. J. Biol. Chem. 259 (1984) 740-748. [PMID: 6693393]

2. Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (–)-linalyl pyrophosphate to (+)- and (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

3. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

4. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

[EC 4.2.3.116 created 2012]

EC 4.2.3.117

Accepted name: (–)-camphene synthase

Reaction: geranyl diphosphate = (–)-camphene + diphosphate

For diagram of reaction click here.

Glossary: (–)-camphene = (1S,4R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane

Other name(s): CS

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (–)-camphene-forming]

Comments: (–)-Camphene is the major product in Abies grandis (grand fir) with traces of other monoterpenoids [1]. In Pseudotsuga menziesii (Douglas-fir) there are about equal parts of (–)-camphene and (–)-α-pinene with traces of four other monoterpenoids [2,3]. In Solanum lycopersicum (tomato) tricyclene, β-myrcene, limonene, and traces of several other monoterpenoids are also formed [4]. See also EC 4.2.3.15 myrcene synthase, EC 4.2.3.16 (4S)-limonene synthase, EC 4.2.3.119 (–)-α-pinene synthase and EC 4.2.3.105 tricyclene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Bohlmann, J., Phillips, M., Ramachandiran, V., Katoh, S. and Croteau, R. cDNA cloning, characterization, and functional expression of four new monoterpene synthase members of the Tpsd gene family from grand fir (Abies grandis). Arch. Biochem. Biophys. 368 (1999) 232-243. [PMID: 10441373]

2. Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427-1439. [PMID: 15921711]

3. Hyatt, D.C. and Croteau, R. Mutational analysis of a monoterpene synthase reaction: altered catalysis through directed mutagenesis of (–)-pinene synthase from Abies grandis. Arch. Biochem. Biophys. 439 (2005) 222-233. [PMID: 15978541]

4. Falara, V., Akhtar, T.A., Nguyen, T.T., Spyropoulou, E.A., Bleeker, P.M., Schauvinhold, I., Matsuba, Y., Bonini, M.E., Schilmiller, A.L., Last, R.L., Schuurink, R.C. and Pichersky, E. The tomato terpene synthase gene family. Plant Physiol. 157 (2011) 770-789. [PMID: 21813655]

[EC 4.2.3.117 created 2012]

EC 4.2.3.118

Accepted name: 2-methylisoborneol synthase

Reaction: (E)-2-methylgeranyl diphosphate + H2O = 2-methylisoborneol + diphosphate

For diagram of reaction click here and mechanism click here.

Other name(s): sco7700; 2-MIB cyclase; MIB synthase; MIBS

Systematic name: (E)-2-methylgeranyl-diphosphate diphosphate-lyase (cyclizing, 2-methylisoborneol-forming)

Comments: The product, 2-methylisoborneol, is a characteristc odiferous compound with a musty smell produced by soil microorganisms.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Wang, C.M. and Cane, D.E. Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. J. Am. Chem. Soc. 130 (2008) 8908-8909. [PMID: 18563898]

2. Komatsu, M., Tsuda, M., Omura, S., Oikawa, H. and Ikeda, H. Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol. Proc. Natl. Acad. Sci. USA 105 (2008) 7422-7427. [PMID: 18492804]

3. Giglio, S., Chou, W.K., Ikeda, H., Cane, D.E. and Monis, P.T. Biosynthesis of 2-methylisoborneol in cyanobacteria. Environ. Sci. Technol. 45 (2011) 992-998. [PMID: 21174459]

[EC 4.2.3.118 created 2012]

EC 4.2.3.119

Accepted name: (–)-α-pinene synthase

Reaction: geranyl diphosphate = (–)-α-pinene + diphosphate

For diagram of reaction click here.

Glossary: (–)-α-pinene = (1S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Other name(s): (–)-α-pinene/(–)-camphene synthase; (–)-α-pinene cyclase

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (–)-α-pinene-forming]

Comments: Cyclase II of Salvia officinalis (sage) gives about equal parts (–)-α-pinene, (–)-β-pinene and (–)-camphene, plus traces of other monoterpenoids. (3S)-Linalyl diphosphate can also be used by the enzyme in preference to (3R)-linalyl diphosphate. The 4-pro-S-hydrogen of geranyl diphosphate is lost. Requires Mg2+ (preferred to Mn2+) [1-6]. The enzyme from Abies grandis (grand fir) gives roughly equal parts (–)-α-pinene and (–)-β-pinene. However the clone ag11 gave 35% (–)-limonene, 24% (–)-α-pinene and 20% (–)-β-phellandrene. It requires Mn2+ and K+ (Mg2+ is ineffective) [7-10]. Synthase I from Pinus taeda (loblolly pine) produces (–)-α-pinene with traces of (–)-β-pinene and requires Mn2+ (preferred to Mg2+) [11,12]. The enzyme from Picea sitchensis (Sika spruce) forms 70% (–)-α-pinene and 30% (–)-β-pinene [13]. The recombinant PmeTPS1 enzyme from Pseudotsuga menziesii (Douglas fir) gave roughly equal proportions of (–)-α-pinene and (–)-camphene plus traces of other monoterpenoids [14]. See also EC 4.2.3.120, (–)-β-pinene synthase; EC 4.2.3.117, (–)-camphene synthase; EC 4.2.3.16, (–)-limonene synthase; and EC 4.2.3.52, (–)-β-phellandrene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Gambliel, H. and Croteau, R. Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. J. Biol. Chem. 259 (1984) 740-748. [PMID: 6693393]

2. Croteau, R.B., Wheeler, C.J., Cane, D.E., Ebert, R. and Ha, H.J. Isotopically sensitive branching in the formation of cyclic monoterpenes: proof that (–)-α-pinene and (–)-β-pinene are synthesized by the same monoterpene cyclase via deprotonation of a common intermediate. Biochemistry 26 (1987) 5383-5389. [PMID: 3314988]

3. Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (–)-linalyl pyrophosphate to (+)- and (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

4. Croteau, R. and Satterwhite, D.M. Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (–)-pinene cyclases from sage. J. Biol. Chem. 264 (1989) 15309-15315. [PMID: 2768265]

5. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

6. Lu, S., Xu, R., Jia, J.W., Pang, J., Matsuda, S.P. and Chen, X.Y. Cloning and functional characterization of a β-pinene synthase from Artemisia annua that shows a circadian pattern of expression. Plant Physiol. 130 (2002) 477-486. [PMID: 12226526]

7. Lewinsohn, E., Gijzen, M. and Croteau, R. Wound-inducible pinene cyclase from grand fir: purification, characterization, and renaturation after SDS-PAGE. Arch. Biochem. Biophys. 293 (1992) 167-173. [PMID: 1731633]

8. Bohlmann, J., Steele, C.L. and Croteau, R. Monoterpene synthases from grand fir (Abies grandis). cDNA isolation, characterization, and functional expression of myrcene synthase, (–)-(4S)-limonene synthase, and (–)-(1S,5S)-pinene synthase. J. Biol. Chem. 272 (1997) 21784-21792. [PMID: 9268308]

9. Bohlmann, J., Phillips, M., Ramachandiran, V., Katoh, S. and Croteau, R. cDNA cloning, characterization, and functional expression of four new monoterpene synthase members of the Tpsd gene family from grand fir (Abies grandis). Arch. Biochem. Biophys. 368 (1999) 232-243. [PMID: 10441373]

10. Hyatt, D.C. and Croteau, R. Mutational analysis of a monoterpene synthase reaction: altered catalysis through directed mutagenesis of (–)-pinene synthase from Abies grandis. Arch. Biochem. Biophys. 439 (2005) 222-233. [PMID: 15978541]

11. Phillips, M.A., Savage, T.J. and Croteau, R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch. Biochem. Biophys. 372 (1999) 197-204. [PMID: 10562434]

12. Phillips, M.A., Wildung, M.R., Williams, D.C., Hyatt, D.C. and Croteau, R. cDNA isolation, functional expression, and characterization of (+)-α-pinene synthase and (–)-α-pinene synthase from loblolly pine (Pinus taeda): stereocontrol in pinene biosynthesis. Arch. Biochem. Biophys. 411 (2003) 267-276. [PMID: 12623076]

13. McKay, S.A., Hunter, W.L., Godard, K.A., Wang, S.X., Martin, D.M., Bohlmann, J. and Plant, A.L. Insect attack and wounding induce traumatic resin duct development and gene expression of (–)-pinene synthase in Sitka spruce. Plant Physiol. 133 (2003) 368-378. [PMID: 12970502]

14. Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427-1439. [PMID: 15921711]

[EC 4.2.3.119 created 2012]

EC 4.2.3.120

Accepted name: (–)-β-pinene synthase

Reaction: geranyl diphosphate = (–)-β-pinene + diphosphate

For diagram of reaction click here.

Glossary: (–)-β-pinene = (1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-2-ene

Other name(s): β-geraniolene synthase; (–)-(1S,5S)-pinene synthase; geranyldiphosphate diphosphate lyase (pinene forming)

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (–)-β-pinene-forming]

Comments: Cyclase II of Salvia officinalis (sage) produces about equal parts (–)-α-pinene, (–)-β-pinene and (–)-camphene, plus traces of other monoterpenoids. The enzyme, which requires Mg2+ (preferred to Mn2+), can also use (3S)-Linalyl diphosphate (preferred to (3R)-linalyl diphosphate) [1-4]. The enzyme from Abies grandis (grand fir) produces roughly equal parts of (–)-α-pinene and (–)-β-pinene [6-9]. Cyclase IV from Pinus contorta (lodgepole pine) produces 63% (–)-β-pinene, 26% 3-carene, and traces of α-pinene [10]. Synthase III from Pinus taeda (loblolly pine) forms (–)-β-pinene with traces of α-pinene and requires Mn2+ and K+ (Mg2+ is ineffective) [11]. A cloned enzyme from Artemisia annua (sweet wormwood) gave (–)-β-pinene with traces of (–)-α-pinene [5]. The enzyme from Picea sitchensis (Sika spruce) forms 30% (–)-β-pinene and 70% (–)-α-pinene [12]. See also EC 4.2.3.119, (–)-α-pinene synthase, EC 4.2.3.117, (–)-camphene synthase, and EC 4.2.3.107 (+)-3-carene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Croteau, R.B., Wheeler, C.J., Cane, D.E., Ebert, R. and Ha, H.J. Isotopically sensitive branching in the formation of cyclic monoterpenes: proof that (–)-α-pinene and (–)-β-pinene are synthesized by the same monoterpene cyclase via deprotonation of a common intermediate. Biochemistry 26 (1987) 5383-5389. [PMID: 3314988]

2. Croteau, R. and Satterwhite, D.M. Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (–)-pinene cyclases from sage. J. Biol. Chem. 264 (1989) 15309-15315. [PMID: 2768265]

3. Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (–)-linalyl pyrophosphate to (+)- and (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

4. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

5. Lu, S., Xu, R., Jia, J.W., Pang, J., Matsuda, S.P. and Chen, X.Y. Cloning and functional characterization of a β-pinene synthase from Artemisia annua that shows a circadian pattern of expression. Plant Physiol. 130 (2002) 477-486. [PMID: 12226526]

6. Gijzen, M., Lewinsohn, E. and Croteau, R. Characterization of the constitutive and wound-inducible monoterpene cyclases of grand fir (Abies grandis). Arch. Biochem. Biophys. 289 (1991) 267-273. [PMID: 1898071]

7. Lewinsohn, E., Gijzen, M. and Croteau, R. Wound-inducible pinene cyclase from grand fir: purification, characterization, and renaturation after SDS-PAGE. Arch. Biochem. Biophys. 293 (1992) 167-173. [PMID: 1731633]

8. Bohlmann, J., Steele, C.L. and Croteau, R. Monoterpene synthases from grand fir (Abies grandis). cDNA isolation, characterization, and functional expression of myrcene synthase, (–)-(4S)-limonene synthase, and (–)-(1S,5S)-pinene synthase. J. Biol. Chem. 272 (1997) 21784-21792. [PMID: 9268308]

9. Hyatt, D.C. and Croteau, R. Mutational analysis of a monoterpene synthase reaction: altered catalysis through directed mutagenesis of (–)-pinene synthase from Abies grandis. Arch. Biochem. Biophys. 439 (2005) 222-233. [PMID: 15978541]

10. Savage, T.J., Ichii, H., Hume, S.D., Little, D.B. and Croteau, R. Monoterpene synthases from gymnosperms and angiosperms: stereospecificity and inactivation by cysteinyl- and arginyl-directed modifying reagents. Arch. Biochem. Biophys. 320 (1995) 257-265. [PMID: 7625832]

11. Phillips, M.A., Savage, T.J. and Croteau, R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch. Biochem. Biophys. 372 (1999) 197-204. [PMID: 10562434]

12. McKay, S.A., Hunter, W.L., Godard, K.A., Wang, S.X., Martin, D.M., Bohlmann, J. and Plant, A.L. Insect attack and wounding induce traumatic resin duct development and gene expression of (–)-pinene synthase in Sitka spruce. Plant Physiol. 133 (2003) 368-378. [PMID: 12970502]

[EC 4.2.3.120 created 2012]

EC 4.2.3.121

Accepted name: (+)-α-pinene synthase

Reaction: geranyl diphosphate = (+)-α-pinene + diphosphate

For diagram of reaction click here.

Glossary: (+)-α-pinene = (1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Other name(s): (+)-α-pinene cyclase; cyclase I

Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-α-pinene-forming]

Comments: Cyclase I of Salvia officinalis (sage) gives about equal parts (+)-α-pinene and (+)-camphene, whereas cyclase III gives about equal parts of (+)-α-pinene and (+)-β-pinene. (3R)-Linalyl diphosphate can also be used by the enzyme in preference to (3S)-linalyl diphosphate. The 4-pro-R-hydrogen of geranyl diphosphate is lost. Requires Mg2+ (preferred to Mn2+) [1-4]. With synthase II of Pinus taeda (loblolly pine) (+)-α-pinene was the only product [5,6]. Requires Mn2+ (preferred to Mg2+). See also EC 4.2.3.122, (+)-β-pinene synthase, and EC 4.2.3.116, (+)-camphene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Gambliel, H. and Croteau, R. Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. J. Biol. Chem. 259 (1984) 740-748. [PMID: 6693393]

2. Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (–)-linalyl pyrophosphate to (+)- and (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

3. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

4. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

5. Phillips, M.A., Savage, T.J. and Croteau, R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch. Biochem. Biophys. 372 (1999) 197-204. [PMID: 10562434]

6. Phillips, M.A., Wildung, M.R., Williams, D.C., Hyatt, D.C. and Croteau, R. cDNA isolation, functional expression, and characterization of (+)-α-pinene synthase and (–)-α-pinene synthase from loblolly pine (Pinus taeda): stereocontrol in pinene biosynthesis. Arch. Biochem. Biophys. 411 (2003) 267-276. [PMID: 12623076]

[EC 4.2.3.121 created 2012]

EC 4.2.3.122

Accepted name: (+)-β-pinene synthase

Reaction: geranyl diphosphate = (+)-β-pinene + diphosphate

For diagram of reaction click here.

Glossary: (+)-β-pinene = (1R,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-2-ene

Other name(s): (+)-pinene cyclase; cyclase III

Systematic name: geranyl-diphosphate diphosphate-lyase [(+)-β-pinene-forming]

Comments: Cyclase III from Salvia officinalis (sage) gives roughly equal parts of (+)-β-pinene and (+)-α-pinene. See EC 4.2.3.121, (+)-α-pinene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

2. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

[EC 4.2.3.122 created 2012]

EC 4.2.3.123

Accepted name: β-sesquiphellandrene synthase

Reaction: (2E,6E)-farnesyl diphosphate = β-sesquiphellandrene + diphosphate

For diagram of reaction click here and mechanism click here.

Other name(s): Tps1; Os08g07100 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, β-sesquiphellandrene-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Zhuang, X., Kollner, T.G., Zhao, N., Li, G., Jiang, Y., Zhu, L., Ma, J., Degenhardt, J. and Chen, F. Dynamic evolution of herbivore-induced sesquiterpene biosynthesis in sorghum and related grass crops. Plant J. 69 (2012) 70-80. [PMID: 21880075]

[EC 4.2.3.123 created 2012]

EC 4.2.3.124

Accepted name: 2-deoxy-scyllo-inosose synthase

Reaction: D-glucose 6-phosphate = 2-deoxy-L-scyllo-inosose + phosphate

For diagram of reaction click here and mechanism click here.

Other name(s): btrC (gene name); neoC (gene name); kanC (gene name)

Systematic name: D-glucose-6-phosphate phosphate-lyase (2-deoxy-L-scyllo-inosose-forming)

Comments: Requires Co2+ [2]. Involved in the biosynthetic pathways of several clinically important aminocyclitol antibiotics, including kanamycin, butirosin, neomycin and ribostamycin. Requires an NAD+ cofactor, which is transiently reduced during the reaction [1,4]. The enzyme from the bacterium Bacillus circulans forms a complex with the glutamine amidotransferase subunit of pyridoxal 5'-phosphate synthase (EC 4.3.3.6), which appears to stabilize the complex [6,7].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Kudo, F., Yamauchi, N., Suzuki, R. and Kakinuma, K. Kinetic isotope effect and reaction mechanism of 2-deoxy-scyllo-inosose synthase derived from butirosin-producing Bacillus circulans. J. Antibiot. (Tokyo) 50 (1997) 424-428. [PMID: 9207913]

2. Kudo, F., Hosomi, Y., Tamegai, H. and Kakinuma, K. Purification and characterization of 2-deoxy-scyllo-inosose synthase derived from Bacillus circulans. A crucial carbocyclization enzyme in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics. J. Antibiot. (Tokyo) 52 (1999) 81-88. [PMID: 10344560]

3. Kudo, F., Tamegai, H., Fujiwara, T., Tagami, U., Hirayama, K. and Kakinuma, K. Molecular cloning of the gene for the key carbocycle-forming enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics and its comparison with dehydroquinate synthase. J. Antibiot. (Tokyo) 52 (1999) 559-571. [PMID: 10470681]

4. Huang, Z., Kakinuma, K. and Eguchi, T. Stereospecificity of hydride transfer in NAD+-catalyzed 2-deoxy-scyllo-inosose synthase, the key enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics. Bioorg. Chem. 33 (2005) 82-89. [PMID: 15788164]

5. Thuy, M.L., Kharel, M.K., Lamichhane, R., Lee, H.C., Suh, J.W., Liou, K. and Sohng, J.K. Expression of 2-deoxy-scyllo-inosose synthase (kanA) from kanamycin gene cluster in Streptomyces lividans. Biotechnol. Lett. 27 (2005) 465-470. [PMID: 15928851]

6. Tamegai, H., Nango, E., Koike-Takeshita, A., Kudo, F. and Kakinuma, K. Significance of the 20-kDa subunit of heterodimeric 2-deoxy-scyllo-inosose synthase for the biosynthesis of butirosin antibiotics in Bacillus circulans. Biosci. Biotechnol. Biochem. 66 (2002) 1538-1545. [PMID: 12224638]

7. Tamegai, H., Sawada, H., Nango, E., Aoki, R., Hirakawa, H., Iino, T. and Eguchi, T. Roles of a 20 kDa protein associated with a carbocycle-forming enzyme involved in aminoglycoside biosynthesis in primary and secondary metabolism. Biosci. Biotechnol. Biochem. 74 (2010) 1215-1219. [PMID: 20530911]

[EC 4.2.3.124 created 2012]

EC 4.2.3.125

Accepted name: α-muurolene synthase

Reaction: (2E,6E)-farnesyl diphosphate = α-muurolene + diphosphate

For diagram of reaction click here.

Other name(s): Cop3

Systematic name: (2E,6E)-farnesyl-diphosphate-diphosphate-lyase (cyclizing, α-muurolene-forming)

Comments: The enzyme has been characterized from the fungus Coprinus cinereus. Also gives germacrene A and γ-muurolene, see EC 4.2.3.23, germacrene-A synthase and EC 4.2.3.126, γ-muurolene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

[EC 4.2.3.125 created 2012]

EC 4.2.3.126

Accepted name: γ-muurolene synthase

Reaction: (2E,6E)-farnesyl diphosphate = γ-muurolene + diphosphate

For diagram of reaction click here.

Glossary: γ-muurolene = (1S,4aS,8aR)-1-isopropyl-7-methyl-4-methylene-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Other name(s): Cop3

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lase (cyclizing, γ-muurolene-forming)

Comments: The enzyme has been characterized from the fungus Coprinus cinereus. Also gives germacrene A and α-muurolene, see EC 4.2.3.23, germacrene-A synthase and EC 4.2.3.125, α-muurolene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

[EC 4.2.3.126 created 2012]

EC 4.2.3.127

Accepted name: β-copaene synthase

Reaction: (2E,6E)-farnesyl diphosphate = β-copaene + diphosphate

For diagram of reaction click here.

Other name(s): cop4

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, β-copaene-forming)

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-cubebene, (+)-sativene and traces of several other sequiterpenoids [1-3]. β-Copaene is formed in the presence of Mg2+ but not Mn2+ [2]. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.128, β-cubebene synthase, and EC 4.2.3.129, (+)-sativene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

3. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

[EC 4.2.3.127 created 2012]

EC 4.2.3.128

Accepted name: β-cubebene synthase

Reaction: (2E,6E)-farnesyl diphosphate = β-cubebene + diphosphate

For diagram of reaction click here.

Other name(s): cop4; Mg25

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, β-cubebene-forming)

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-copaene, (+)-sativene and traces of several other sequiterpenoids [2-4]. It is found in many higher plants such as Magnolia grandiflora (Southern Magnolia) together with germacrene A [1]. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.127, β-copaene synthase, EC 4.2.3.129, (+)-sativene synthase, and EC 4.2.3.23, germacrene A synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Lee, S. and Chappell, J. Biochemical and genomic characterization of terpene synthases in Magnolia grandiflora. Plant Physiol. 147 (2008) 1017-1033. [PMID: 18467455]

2. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

3. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

4. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

[EC 4.2.3.128 created 2012]

EC 4.2.3.129

Accepted name: (+)-sativene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (+)-sativene + diphosphate

For diagram of reaction click here.

Other name(s): cop4

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-sativene-forming)

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-copaene, β-cubebene, and traces of several other sequiterpenoids. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.127, β-copaene synthase, and EC 4.2.3.128, β-cubebene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

3. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

[EC 4.2.3.129 created 2012]

EC 4.2.3.130

Accepted name: tetraprenyl-β-curcumene synthase

Reaction: all-trans-heptaprenyl diphosphate = tetraprenyl-β-curcumene + diphosphate

For diagram of reaction click here.

Other name(s): ytpB (gene name)

Systematic name: all-trans-heptaprenyl-diphosphate diphosphate-lyase (cyclizing, tetraprenyl-β-curcumene-forming)

Comments: Isolated from Bacillus subtilis. This sesquarterpene is present in a number of Bacillus species.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Sato, T., Yoshida, S., Hoshino, H., Tanno, M., Nakajima, M. and Hoshino, T. Sesquarterpenes (C35 terpenes) biosynthesized via the cyclization of a linear C35 isoprenoid by a tetraprenyl-β-curcumene synthase and a tetraprenyl-β-curcumene cyclase: identification of a new terpene cyclase. J. Am. Chem. Soc. 133 (2011) 9734-9737. [PMID: 21627333]

[EC 4.2.3.130 created 2012]

EC 4.2.3.131

Accepted name: miltiradiene synthase

Reaction: (+)-copalyl diphosphate = miltiradiene + diphosphate

For diagram of reaction click here.

Other name(s): SmMDS; SmiKSL; RoKSL

Systematic name: (+)-copalyl-diphosphate diphosphate-lyase (cyclizing, miltiradiene-forming)

Comments: Isolated from the plants Rosmarinus officinalis (rosemary) and Salvia miltiorrhiza. The enzyme from the plant Selaginella moellendorffii is mutifunctional and also catalyses EC 5.5.1.12, copalyl diphosphate synthase [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Gao, W., Hillwig, M.L., Huang, L., Cui, G., Wang, X., Kong, J., Yang, B. and Peters, R.J. A functional genomics approach to tanshinone biosynthesis provides stereochemical insights. Org. Lett. 11 (2009) 5170-5173. [PMID: 19905026]

2. Sugai, Y., Ueno, Y., Hayashi, K., Oogami, S., Toyomasu, T., Matsumoto, S., Natsume, M., Nozaki, H. and Kawaide, H. Enzymatic 13C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii. J. Biol. Chem. 286 (2011) 42840-42847. [PMID: 22027823]

3. Bruckner, K., Bozic, D., Manzano, D., Papaefthimiou, D., Pateraki, I., Scheler, U., Ferrer, A., de Vos, R.C., Kanellis, A.K. and Tissier, A. Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes. Phytochemistry 101 (2014) 52-64. [PMID: 24569175]

[EC 4.2.3.131 created 2012]

EC 4.2.3.132

Accepted name: neoabietadiene synthase

Reaction: (+)-copalyl diphosphate = neoabietadiene + diphosphate

For diagram of reaction click here.

Glossary: neoabietadiene = abieta-8(14),13(15)-diene

Other name(s): AgAS; PtTPS-LAS

Systematic name: (+)-copaly-diphosphate diphosphate-lyase (cyclizing, neoabietadiene-forming)

Comments: Isolated from Abies grandis (grand fir) [1]. This class I enzyme forms about equal proportions of abietadiene, levopimaradiene and neoabietadiene. See also EC 4.2.3.18, abieta-7,13-diene synthase and EC 4.2.3.32, levopimaradiene synthase. An X-ray study of this multifunctional enzyme showed that the class I activity is in the α domain, while (+)-copalyl diphosphate synthase activity (EC 5.5.1.12, a class II activity) is in the β and γ domains [2]. In Pinus taeda (loblolly pine) the major product is levopimaradiene, with less abietadiene and neoabietadiene [3].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Peters, R.J., Flory, J.E., Jetter, R., Ravn, M.M., Lee, H.J., Coates, R.M. and Croteau, R.B. Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme. Biochemistry 39 (2000) 15592-15602. [PMID: 11112547]

2. Zhou, K., Gao, Y., Hoy, J.A., Mann, F.M., Honzatko, R.B. and Peters, R.J. Insights into diterpene cyclization from structure of bifunctional abietadiene synthase from Abies grandis. J. Biol. Chem. 287 (2012) 6840-6850. [PMID: 22219188]

3. Ro, D.K. and Bohlmann, J. Diterpene resin acid biosynthesis in loblolly pine (Pinus taeda): functional characterization of abietadiene/levopimaradiene synthase (PtTPS-LAS) cDNA and subcellular targeting of PtTPS-LAS and abietadienol/abietadienal oxidase (PtAO, CYP720B1). Phytochemistry 67 (2006) 1572-1578. [PMID: 16497345]

[EC 4.2.3.132 created 2012]

EC 4.2.3.133

Accepted name: α-copaene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (–)-α-copaene + diphosphate

For diagram of reaction click here.

Glossary: (–)-α-copaene = (1R,2S,6S,7S,8S)-1,3-dimethyl-8-(propan-2-yl)tricyclo[4.4.0.02,7]dec-3-ene
For diagram of the structures of α-copaene and β-copaene, click here

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, α-copaene-forming)

Comments: Isolated from Helianthus annuus (sunflower). The enzyme also produces β-caryophyllene, δ-cadinene and traces of other sesquiterpenoids. See EC 4.2.3.13 (+)-δ-cadinene synthase, EC 4.2.3.57 (–)-β-caryophyllene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Gopfert, J.C., Macnevin, G., Ro, D.K. and Spring, O. Identification, functional characterization and developmental regulation of sesquiterpene synthases from sunflower capitate glandular trichomes. BMC Plant Biol. 9 (2009) 86. [PMID: 19580670]

2. Xie, X., Kirby, J. and Keasling, J.D. Functional characterization of four sesquiterpene synthases from Ricinus communis (castor bean). Phytochemistry 78 (2012) 20-28. [PMID: 22459969]

[EC 4.2.3.133 created 2012]

EC 4.2.3.134

Accepted name: 5-phosphooxy-L-lysine phospho-lyase

Reaction: (5R)-5-phosphooxy-L-lysine + H2O = (S)-2-amino-6-oxohexanoate + NH3 + phosphate

Other name(s): 5-phosphohydroxy-L-lysine ammoniophospholyase; AGXT2L2 (gene name); 5-phosphonooxy-L-lysine phospho-lyase; (5R)-5-phosphonooxy-L-lysine phosphate-lyase (deaminating; (S)-2-amino-6-oxohexanoate-forming)

Systematic name: (5R)-5-phosphooxy-L-lysine phosphate-lyase (deaminating; (S)-2-amino-6-oxohexanoate-forming)

Comments: A pyridoxal-phosphate protein. Has no activity with phosphoethanolamine (cf. EC 4.2.3.2, ethanolamine-phosphate phospho-lyase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Tsai, C.H. and Henderson, L.M. Degradation of O-phosphohydroxylysine by rat liver. Purification of the phospho-lyase. J. Biol. Chem. 249 (1974) 5784-5789. [PMID: 4412716]

2. Veiga-da-Cunha, M., Hadi, F., Balligand, T., Stroobant, V. and Van Schaftingen, E. Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine. J. Biol. Chem. 287 (2012) 7246-7255. [PMID: 22241472]

[EC 4.2.3.134 created 2012]

EC 4.2.3.135

Accepted name: Δ6-protoilludene synthase

Reaction: (2E,6E)-farnesyl diphosphate = Δ6-protoilludene + diphosphate

For diagram of reaction click here.

Glossary: Δ6-protoilludene = (4aS,7aS,7bR)-3,6,6,7b-tetramethyl-2,4,4a,5,6,7,7a,7b-octahydro-1H-cyclobuta[1,2-e]indene

Other name(s): 6-protoilludene synthase

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, Δ6-protoilludene-forming)

Comments: Isolated from the fungus Armillaria gallica. Δ6-Protoilludene is the first step in the biosynthesis of the melleolides.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Engels, B., Heinig, U., Grothe, T., Stadler, M. and Jennewein, S. Cloning and characterization of an Armillaria gallica cDNA encoding protoilludene synthase, which catalyzes the first committed step in the synthesis of antimicrobial melleolides. J. Biol. Chem. 286 (2011) 6871-6878. [PMID: 21148562]

[EC 4.2.3.135 created 2012]

EC 4.2.3.136

Accepted name: α-isocomene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (–)-α-isocomene + diphosphate

For diagram of reaction click here.

Glossary: (–)-α-isocomene = (1R,3aS,5aS,8aR)-1,3a,4,5a-tetramethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene

Other name(s): MrTPS2

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (–)-α-isocomene-forming)

Comments: Isolated from the roots of the plant Matricaria chamomilla var. recutita (chamomile). The enzyme also produced traces of five other sesquiterpenoids.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Irmisch, S., Krause, S.T., Kunert, G., Gershenzon, J., Degenhardt, J. and Kollner, T.G. The organ-specific expression of terpene synthase genes contributes to the terpene hydrocarbon composition of chamomile essential oils. BMC Plant Biol. 12 (2012) 84. [PMID: 22682202]

[EC 4.2.3.136 created 2012]

EC 4.2.3.137

Accepted name: (E)-2-epi-β-caryophyllene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (E)-2-epi-β-caryophyllene + diphosphate

Other name(s): 2-epi-(E)-β-caryophyllene synthase; SmMTPSL26

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (E)-2-epi-β-caryophyllene-forming)

Comments: Isolated from the plant Selaginella moellendorfii. The enzyme also gives two other sesquiterpenoids.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Li, G., Kollner, T.G., Yin, Y., Jiang, Y., Chen, H., Xu, Y., Gershenzon, J., Pichersky, E. and Chen, F. Nonseed plant Selaginella moellendorfii has both seed plant and microbial types of terpene synthases. Proc. Natl. Acad. Sci. USA 109 (2012) 14711-14715. [PMID: 22908266]

[EC 4.2.3.137 created 2012]

EC 4.2.3.138

Accepted name: (+)-epi-α-bisabolol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-epi-α-bisabolol + diphosphate

For diagram of reaction click here.

Glossary: (+)-epi-α-bisabolol = (2S)-6-methyl-2-[(1R)-4-methylcyclohex-3-en-1-yl]hept-5-en-2-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-epi-α-bisabolol-forming)

Comments: Isolated from the plant Phyla dulcis (Aztec sweet herb). (+)-epi-α-Bisabolol is the precursor of the sweetener hernandulcin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Attia, M., Kim, S.U. and Ro, D.K. Molecular cloning and characterization of (+)-epi-α-bisabolol synthase, catalyzing the first step in the biosynthesis of the natural sweetener, hernandulcin, in Lippia dulcis. Arch. Biochem. Biophys. 527 (2012) 37-44. [PMID: 22867794]

[EC 4.2.3.138 created 2012]

EC 4.2.3.139

Accepted name: valerena-4,7(11)-diene synthase

Reaction: (2E,6E)-farnesyl diphosphate = valerena-4,7(11)-diene + diphosphate

For diagram of reaction click here.

Glossary: valerena-4,7(11)-diene = (4S,7R,7aR)-3,7-dimethyl-4-(2-methylprop-1-en-1-yl)-2,4,5,6,7,7a-hexahydro-1H-indene

Other name(s): VoTPS2; VoTPS7

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, valerena-4,7(11)-diene-forming)

Comments: Isolated from the plant Valeriana officinalis (valerian). Note that due to a different numbering system the product is also known as valerena-1,10-diene.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Pyle, B.W., Tran, H.T., Pickel, B., Haslam, T.M., Gao, Z., Macnevin, G., Vederas, J.C., Kim, S.U. and Ro, D.K. Enzymatic synthesis of valerena-4,7(11)-diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis). FEBS J. 279 (2012) 3136-3146. [PMID: 22776156]

2. Yeo, Y.S., Nybo, S.E., Chittiboyina, A.G., Weerasooriya, A.D., Wang, Y.H., Gongora-Castillo, E., Vaillancourt, B., Buell, C.R., DellaPenna, D., Celiz, M.D., Jones, A.D., Wurtele, E.S., Ransom, N., Dudareva, N., Shaaban, K.A., Tibrewal, N., Chandra, S., Smillie, T., Khan, I.A., Coates, R.M., Watt, D.S. and Chappell, J. Functional identification of valerena-1,10-diene synthase, a terpene synthase catalyzing a unique chemical cascade in the biosynthesis of biologically active sesquiterpenes in Valeriana officinalis. J. Biol. Chem. 288 (2013) 3163-3173. [PMID: 23243312]

[EC 4.2.3.139 created 2012]

EC 4.2.3.140

Accepted name: cis-abienol synthase

Reaction: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate = cis-abienol + diphosphate

For diagram of reaction click here.

Glossary: cis-abienol = (12Z)-labda-12,14-dien-8α-ol
(13E)-8α-hydroxylabd-13-en-15-yl diphosphate = 8-hydroxycopalyl diphosphate

Other name(s): Z-abienol synthase; CAS; ABS

Systematic name: (13E)-8α-hydroxylabd-13-en-15-yl-diphosphate-lyase (cis-abienol forming)

Comments: Isolated from the plants Abies balsamea (balsam fir) [1] and Nicotiana tabacum (tobacco) [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Zerbe, P., Chiang, A., Yuen, M., Hamberger, B., Hamberger, B., Draper, J.A., Britton, R. and Bohlmann, J. Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production. J. Biol. Chem. 287 (2012) 12121-12131. [PMID: 22337889]

2. Sallaud, C., Giacalone, C., Topfer, R., Goepfert, S., Bakaher, N., Rosti, S. and Tissier, A. Characterization of two genes for the biosynthesis of the labdane diterpene Z-abienol in tobacco (Nicotiana tabacum) glandular trichomes. Plant J. 72 (2012) 1-17. [PMID: 22672125]

[EC 4.2.3.140 created 2012]

EC 4.2.3.141

Accepted name: sclareol synthase

Reaction: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate + H2O = sclareol + diphosphate

For diagram of reaction click here.

Glossary: sclareol = (13R)-labd-14-ene-8α,13-diol
(13E)-8α-hydroxylabd-13-en-15-yl diphosphate = copal-8-ol diphosphate

Other name(s): SS

Systematic name: (13E)-8α-hydroxylabd-13-en-15-yl-diphosphate-lyase (sclareol forming)

Comments: Isolated from the plant Salvia sclarea (clary sage). Originally thought to be synthesized in one step from geranylgeranyl diphosphate it is now known to require two enzymes, EC 4.2.1.133, copal-8-ol diphosphate synthase and EC 4.2.3.141, sclareol synthase. Sclareol is used in perfumery.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Caniard, A., Zerbe, P., Legrand, S., Cohade, A., Valot, N., Magnard, J.L., Bohlmann, J. and Legendre, L. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol. 12:119 (2012) . [PMID: 22834731]

[EC 4.2.3.141 created 2013]

EC 4.2.3.142

Accepted name: 7-epizingiberene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]

Reaction: (2Z,6Z)-farnesyl diphosphate = 7-epizingiberene + diphosphate

For diagram of reaction click here.

Glossary: 7-epizingiberene = (5R)-2-methyl-5-[(2R)-6-methylhept-5-en-2-yl]cyclohexa-1,3-diene

Other name(s): ShZIS (gene name)

Systematic name: (2Z,6Z)-farnesyl-diphosphate lyase (cyclizing; 7-epizingiberene-forming)

Comments: Isolated from the plant Solanum habrochaites. 7-Epizingiberene is a whitefly repellant.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Bleeker, P.M., Mirabella, R., Diergaarde, P.J., Vandoorn, A., Tissier, A., Kant, M.R., Prins, M., de Vos, M., Haring, M.A. and Schuurink, R.C. Improved herbivore resistance in cultivated tomato with the sesquiterpene biosynthetic pathway from a wild relative. Proc. Natl. Acad. Sci. USA 109 (2012) 20124-20129. [PMID: 23169639]

[EC 4.2.3.142 created 2013]

EC 4.2.3.143

Accepted name: kunzeaol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = kunzeaol + diphosphate

For diagram of reaction click here.

Glossary: kunzeaol = 6β-hydroxygermacra-1(10),4-diene = (1R,2E,6E,10R)-3,7-dimethyl-10-isopropylcyclodeca-2,6-dienol

Other name(s): TgTPS2 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (kunzeaol forming)

Comments: Isolated from the root of the plant Thapsia garganica. The enzyme also produces germacrene D, bicyclogermacrene and traces of other sesquiterpenoids. See EC 4.2.3.77, (+)-germacrene D synthase and EC 4.2.3.100, bicyclogermacrene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Pickel, B., Drew, D.P., Manczak, T., Weitzel, C., Simonsen, H.T. and Ro, D.K. Identification and characterization of a kunzeaol synthase from Thapsia garganica: implications for the biosynthesis of the pharmaceutical thapsigargin. Biochem. J. 448 (2012) 261-271. [PMID: 22938155]

[EC 4.2.3.143 created 2013]

EC 4.2.3.144

Accepted name: geranyllinalool synthase

Reaction: geranylgeranyl diphosphate + H2O = (E,E)-geranyllinalool + diphosphate

For diagram of reaction click here.

Glossary: geranylgeranyl diphosphate = (2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl diphosphate
(E,E)-geranyllinalool = (6E,10E)-3,7,11,15-tetramethylhexadeca-1,6,10,14-tetraen-3-ol

Other name(s): TPS04/GES; GES

Systematic name: geranylgeranyl diphosphate diphosphate-lyase ((E,E)-geranyllinalool-forming)

Comments: The enzyme is a component of the herbivore-induced indirect defense system. The product, (E,E)-geranyllinalool, is a precursor to the volatile compound 4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT), which is released by many plants in response to damage.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Herde, M., Gartner, K., Kollner, T.G., Fode, B., Boland, W., Gershenzon, J., Gatz, C. and Tholl, D. Identification and regulation of TPS04/GES, an Arabidopsis geranyllinalool synthase catalyzing the first step in the formation of the insect-induced volatile C16-homoterpene TMTT. Plant Cell 20 (2008) 1152-1168. [PMID: 18398052]

2. Attaran, E., Rostas, M. and Zeier, J. Pseudomonas syringae elicits emission of the terpenoid (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene in Arabidopsis leaves via jasmonate signaling and expression of the terpene synthase TPS4. Mol Plant Microbe Interact 21 (2008) 1482-1497. [PMID: 18842097]

[EC 4.2.3.144 created 2013]

EC 4.2.3.145

Accepted name: ophiobolin F synthase

Reaction: (2E,6E,10E,14E)-geranylfarnesyl diphosphate + H2O = ophiobolin F + diphosphate

For diagram of reaction click here.

Systematic name: (2E,6E,10E,14E)-geranylfarnesyl-diphosphate diphosphate-lyase (cyclizing, ophiobolin-F-forming)

Comments: Isolated from the fungus Aspergillus clavatus. The product is a sesterterpenoid (C25 terpenoid).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Chiba, R., Minami, A., Gomi, K. and Oikawa, H. Identification of ophiobolin F synthase by a genome mining approach: a sesterterpene synthase from Aspergillus clavatus. Org. Lett. 15 (2013) 594-597. [PMID: 23324037]

[EC 4.2.3.145 created 2014]

EC 4.2.3.146

Accepted name: cyclooctat-9-en-7-ol synthase

Reaction: geranylgeranyl diphosphate + H2O = cyclooctat-9-en-7-ol + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: cyclooctat-9-en-7-ol = (1S,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulen-4-ol

Other name(s): cetB2

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclooctat-9-en-7-ol-forming)

Comments: Requires Mg2+. Isolated from the bacterium Streptomyces melanosporofaciens, where it is part of the biosynthesis of cyclooctatin, a potent inhibitor of lysophospholipase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736-743. [PMID: 19635410]

2. Zhang, X., Shang, G., Gu, L. and Shen, Y. Crystallization and preliminary X-ray diffraction analysis of the diterpene cyclooctatin synthase (CYC) from Streptomyces sp. LZ35. Acta Crystallogr. F Struct. Biol. Commun. 70 (2014) 366-369. [PMID: 24598929]

[EC 4.2.3.146 created 2014]

EC 4.2.3.147

Accepted name: pimaradiene synthase

Reaction: (+)-copalyl diphosphate = pimara-8(14),15-diene + diphosphate

For diagram of reaction click here.

Other name(s): PbmPIM1; PcmPIM1

Systematic name: (+)-copalyl diphosphate-lyase (pimara-8(14),15-diene-forming)

Comments: Isolated from the plants Pinus banksiana (jack pine) and Pinus contorta (lodgepole pine).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Hall, D.E., Zerbe, P., Jancsik, S., Quesada, A.L., Dullat, H., Madilao, L.L., Yuen, M. and Bohlmann, J. Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases. Plant Physiol. 161 (2013) 600-616. [PMID: 23370714]

[EC 4.2.3.147 created 2014]

EC 4.2.3.148

Accepted name: cembrene C synthase

Reaction: geranylgeranyl diphosphate = cembrene C + diphosphate

For diagram of reaction click here.

Glossary: cembrene C = (1E,5E,9E)-1,5,9-trimethyl-12-(propan-2-ylidene)cyclotetradeca-1,5,9-triene

Other name(s): DtcycA (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cembrene-C-forming)

Comments: Requires Mg2+. Isolated from the bacterium Streptomyces sp. SANK 60404. This bifunctional enzyme also produces (R)-nephthenol. See EC 4.2.3.149, nephthenol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. Chembiochem 14 (2013) 316-321. [PMID: 23386483]

[EC 4.2.3.148 created 2014]

EC 4.2.3.149

Accepted name: nephthenol synthase

Reaction: geranylgeranyl diphosphate + H2O = (R)-nephthenol + diphosphate

For diagram of reaction click here.

Glossary: (R)-nephthenol = 2-[(1R,3E,7E,11E)-4,8,12-trimethyltetradeca-3,7,11-trien-1-yl]propan-2-ol

Other name(s): DtcycA (gene name); DtcycB (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [(R)-nephthenol-forming]

Comments: Requires Mg2+. Two isozymes with this activity were isolated from the bacterium Streptomyces sp. SANK 60404. The enzyme encoded by the DtcycA gene also produces cembrene C (see EC 4.2.3.148, cembrene C synthase), while the enzyme encoded by the DtcycB gene also produces (R)-cembrene A and (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol (see EC 4.2.3.150, cembrene A synthase, and EC 4.2.3.151, pentamethylcyclopentadecatrienol synthase).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. Chembiochem 14 (2013) 316-321. [PMID: 23386483]

[EC 4.2.3.149 created 2014]

EC 4.2.3.150

Accepted name: cembrene A synthase

Reaction: geranylgeranyl diphosphate = (R)-cembrene A + diphosphate

For diagram of reaction click here.

Glossary: cembrene A = (1E,5E,9E,12R)-1,5,9-trimethyl-12-(propan-2-en-2-yl)cyclotetradeca-1,5,9-triene

Other name(s): DtcycB (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [(R)-cembrene-A-forming]

Comments: Requires Mg2+. Isolated from the bacterium Streptomyces sp. SANK 60404. This trifunctional enzyme, which contains a [4Fe-4S] cluster, also produces (R)-nephthenol and (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol. See EC 4.2.3.149, nephthenol synthase and EC 4.2.3.151, pentamethylcyclopentadecatrienol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. Chembiochem 14 (2013) 316-321. [PMID: 23386483]

[EC 4.2.3.150 created 2014]

EC 4.2.3.151

Accepted name: pentamethylcyclopentadecatrienol synthase

Reaction: geranylgeranyl diphosphate + H2O = (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol + diphosphate

For diagram of reaction click here.

Other name(s): DtcycB (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [(1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol-forming]

Comments: Requires Mg2+. Isolated from the bacterium Streptomyces sp. SANK 60404. This trifunctional enzyme, which contains a [4Fe-4S] cluster, also produces (R)-nephthenol and (R)-cembrene A. See EC 4.2.3.150, cembrene A synthase and EC 4.2.3.149, nephthenol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. Chembiochem 14 (2013) 316-321. [PMID: 23386483]

[EC 4.2.3.151 created 2014]

EC 4.2.3.152

Accepted name: 2-epi-5-epi-valiolone synthase

Reaction: α-D-sedoheptulopyranose 7-phosphate = 2-epi-5-epi-valiolone + phosphate

For diagram of reaction click here.

Glossary: 2-epi-5-epi-valiolone = (2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohexan-1-one

Other name(s): AcbC; ValA; CetA; SalQ; C7-cyclitol synthase

Systematic name: α-D-sedoheptulopyranose-7-phosphate phosphate-lyase (cyclizing; 2-epi-5-epi-valiolone-forming)

Comments: The enzyme is highly specific for α-D-sedoheptulopyranose 7-phosphate. It requires a divalent metal ion (Zn2+ or Co2+) and an NAD+ cofactor, which is transiently reduced during the reaction.The enzyme is involved in the biosynthesis of C7N-aminocyclitol natural products, such as the valienamine moiety of the antidiabetic drug acarbose and the crop protectant validamycin A. cf. EC 4.2.3.155, 2-epi-valiolone synthase and EC 4.2.3.154, desmethyl-4-deoxygadusol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Stratmann, A., Mahmud, T., Lee, S., Distler, J., Floss, H.G. and Piepersberg, W. The AcbC protein from Actinoplanes species is a C7-cyclitol synthase related to 3-dehydroquinate synthases and is involved in the biosynthesis of the α-glucosidase inhibitor acarbose. J. Biol. Chem. 274 (1999) 10889-10896. [PMID: 10196166]

2. Yu, Y., Bai, L., Minagawa, K., Jian, X., Li, L., Li, J., Chen, S., Cao, E., Mahmud, T., Floss, H.G., Zhou, X. and Deng, Z. Gene cluster responsible for validamycin biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008. Appl. Environ. Microbiol. 71 (2005) 5066-5076. [PMID: 16151088]

3. Wu, X., Flatt, P.M., Schlorke, O., Zeeck, A., Dairi, T. and Mahmud, T. A comparative analysis of the sugar phosphate cyclase superfamily involved in primary and secondary metabolism. Chembiochem 8 (2007) 239-248. [PMID: 17195255]

4. Choi, W.S., Wu, X., Choeng, Y.H., Mahmud, T., Jeong, B.C., Lee, S.H., Chang, Y.K., Kim, C.J. and Hong, S.K. Genetic organization of the putative salbostatin biosynthetic gene cluster including the 2-epi-5-epi-valiolone synthase gene in Streptomyces albus ATCC 21838. Appl. Microbiol. Biotechnol. 80 (2008) 637-645. [PMID: 18648803]

5. Kean, K.M., Codding, S.J., Asamizu, S., Mahmud, T. and Karplus, P.A. Structure of a sedoheptulose 7-phosphate cyclase: ValA from Streptomyces hygroscopicus. Biochemistry 53 (2014) 4250-4260. [PMID: 24832673]

[EC 4.2.3.152 created 2015, modified 2016]

EC 4.2.3.153

Accepted name: (5-formylfuran-3-yl)methyl phosphate synthase

Reaction: (5-formylfuran-3-yl)methyl phosphate + phosphate + 2 H2O = 2 D-glyceraldehyde 3-phosphate

For diagram of reaction click here.

Glossary: (5-formylfuran-3-yl)methyl phosphate = 4-(hydroxymethyl)furan-2-carboxaldehyde phosphate

Other name(s): mfnB (gene name); 4-HFC-P synthase; 4-(hydroxymethyl)-2-furaldehyde phosphate synthase

Systematic name: D-glyceraldehyde-3-phosphate phosphate-lyase [D-glyceraldehyde-3-phosphate-adding; (5-formylfuran-3-yl)methyl-phosphate-forming]

Comments: The enzyme catalyses the reaction in the direction of producing (5-formylfuran-3-yl)methyl phosphate, an intermediate in the biosynthesis of methanofuran. The sequence of events starts with the removal of a phosphate group, followed by aldol condensation and cyclization. Methanofuran is a carbon-carrier cofactor involved in the first step of the methanogenic reduction of carbon dioxide by methanogenic archaea.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Miller, D., Wang, Y., Xu, H., Harich, K. and White, R.H. Biosynthesis of the 5-(aminomethyl)-3-furanmethanol moiety of methanofuran. Biochemistry 53 (2014) 4635-4647. [PMID: 24977328]

2. Bobik, T.A., Morales, E.J., Shin, A., Cascio, D., Sawaya, M.R., Arbing, M., Yeates, T.O. and Rasche, M.E. Structure of the methanofuran/methanopterin-biosynthetic enzyme MJ1099 from Methanocaldococcus jannaschii. Acta Crystallogr. F Struct. Biol. Commun. 70 (2014) 1472-1479. [PMID: 25372812]

3. Wang, Y., Jones, M.K., Xu, H., Ray, W.K. and White, R.H. Mechanism of the enzymatic synthesis of 4-(hydroxymethyl)-2-furancarboxaldehyde-phosphate (4-HFC-P) from glyceraldehyde-3-phosphate catalyzed by 4-HFC-P synthase. Biochemistry 54 (2015) 2997-3008. [PMID: 25905665]

[EC 4.2.3.153 created 2015 as EC 4.1.99.21, transferred 2015 to EC 4.2.3.153]

EC 4.2.3.154

Accepted name: demethyl-4-deoxygadusol synthase

Reaction: D-sedoheptulose 7-phosphate = demethyl-4-deoxygadusol + phosphate + H2O

For diagram of reaction click here.

Glossary: demethyl-4-deoxygadusol = 2,3,5-trihydroxy-5-(hydroxymethyl)cyclohex-2-en-1-one

Other name(s): Nos2 (gene name); Anb2 (gene name)

Systematic name: D-sedoheptulose-7-phosphate phosphate-lyase (cyclizing; demethyl-4-deoxygadusol-forming)

Comments: The enzyme, characterized from the cyanobacterium Nostoc punctiforme PCC 73102, is involved in the biosynthesis of the sunscreen compound shinorine. It requires a divalent metal ion (Zn2+ or Co2+) and an NAD+ cofactor, which is transiently reduced during the reaction. cf. EC 4.2.3.152, 2-epi-5-epi-valiolone synthase and EC 4.2.3.155, 2-epi-valiolone synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Balskus, E.P. and Walsh, C.T. The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria. Science 329 (2010) 1653-1656. [PMID: 20813918]

2. Asamizu, S., Xie, P., Brumsted, C.J., Flatt, P.M. and Mahmud, T. Evolutionary divergence of sedoheptulose 7-phosphate cyclases leads to several distinct cyclic products. J. Am. Chem. Soc. 134 (2012) 12219-12229. [PMID: 22741921]

[EC 4.2.3.154 created 2016]

EC 4.2.3.155

Accepted name: 2-epi-valiolone synthase

Reaction: D-sedoheptulose 7-phosphate = 2-epi-valiolone + phosphate

For diagram of reaction click here.

Glossary: 2-epi-valiolone = (2S,3S,4S,5S)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohexan-1-one

Systematic name: D-sedoheptulose-7-phosphate phosphate-lyase (cyclizing; 2-epi-valiolone-forming)

Comments: The enzyme, characterized from the bacteria Actinosynnema mirum and Stigmatella aurantiaca DW4/3-1, produces 2-epi-valiolone, which is believed to function as a precursor in aminocyclitol biosynthesis. It requires a divalent metal ion (Zn2+ or Co2+) and an NAD+ cofactor, which is transiently reduced during the reaction. cf. EC 4.2.3.152, 2-epi-5-epi-valiolone synthase and EC 4.2.3.154, desmethyl-4-deoxygadusol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Asamizu, S., Xie, P., Brumsted, C.J., Flatt, P.M. and Mahmud, T. Evolutionary divergence of sedoheptulose 7-phosphate cyclases leads to several distinct cyclic products. J. Am. Chem. Soc. 134 (2012) 12219-12229. [PMID: 22741921]

[EC 4.2.3.155 created 2016]

EC 4.2.3.156

Accepted name: hydroxysqualene synthase

Reaction: presqualene diphosphate + H2O = hydroxysqualene + diphosphate

For diagram of reaction click here.

Glossary: hydroxysqualene = (6E,10E,12R,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-12-ol

Other name(s): hpnC (gene name)

Systematic name: presqualene diphosphate diphosphate-lyase (adding water; hydroxyasqualene-forming)

Comments: This enzyme, isolated from the bacteria Rhodopseudomonas palustris and Zymomonas mobilis, participates, along with EC 2.5.1.103, presqualene diphosphate synthase, and EC 1.17.8.1, hydroxysqualene dehydroxylase, in the conversion of all-trans-farnesyl diphosphate to squalene. Eukaryotes achieve the same goal in a single step, catalysed by EC 2.5.1.21, squalene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Pan, J.J., Solbiati, J.O., Ramamoorthy, G., Hillerich, B.S., Seidel, R.D., Cronan, J.E., Almo, S.C. and Poulter, C.D. Biosynthesis of squalene from farnesyl diphosphate in bacteria: three steps catalyzed by three enzymes. ACS Cent Sci 1 (2015) 77-82. [PMID: 26258173]

[EC 4.2.3.156 created 2016]

EC 4.2.3.157

Accepted name: (+)-isoafricanol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-isoafricanol + diphosphate

For diagram of reaction click here.

Glossary: (+)-isoafricanol = (1aS,4aR,5R,7aS,7bR)-3,3,5,7b-tetramethyldecahydro-4aH-cyclopropa[e]azulen-4a-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-isoafricanol-forming]

Comments: (+)-Isoafricanol is a sesquiterpene alcohol. Its synthesis has been shown to occur in the bacteria Streptomyces violaceusniger and Streptomyces malaysiensis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Riclea, R., Citron, C.A., Rinkel, J. and Dickschat, J.S. Identification of isoafricanol and its terpene cyclase in Streptomyces violaceusniger using CLSA-NMR. Chem. Commun. (Camb.) 50 (2014) 4228-4230. [PMID: 24626486]

2. Rabe, P., Samborskyy, M., Leadlay, P.F. and Dickschat, J.S. Isoafricanol synthase from Streptomyces malaysiensis. Org. Biomol. Chem. 15 (2017) 2353-2358. [PMID: 28247907]

[EC 4.2.3.157 created 2017]

EC 4.2.3.158

Accepted name: (–)-spiroviolene synthase

Reaction: geranylgeranyl diphosphate = (–)-spiroviolene + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: (–)-spiroviolene = (2R,3a'S,3b'R,5R,6a'R)-2,4',4',5,6a'-pentamethyl-2',3',3a',3b',4',5',6',6a'-octahydrospiro[cyclopentane-1,1'-cyclopenta[a]pentalene]

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [cyclizing, (–)-spiroviolene-forming]

Comments: The enzyme, which forms the diterpene (–)-spiroviolene, has been characterized from the bacterium Streptomyces violens.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Rinkel, J., Dolja, E., Schmitz, T., Nubbemeyer, B., Luu, T.H. and Dickschat, J.S. Mechanistic investigations of two bacterial diterpene cyclases: spiroviolene synthase and tsukubadiene synthase. Angew. Chem. Int. Ed. Engl. 56 (2017) 2776-2779. [PMID: 28146322]

[EC 4.2.3.158 created 2017]

EC 4.2.3.159

Accepted name: tsukubadiene synthase

Reaction: geranylgeranyl diphosphate = tsukubadiene + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: tsukubadiene = (1S,3aS,5Z,7aS,10aR,11Z)-1,5,8,8,10a-pentamethyl-2,3,3a,4,7,7a,8,9,10,10a-decahydro-1H-dicyclopenta[a,d][9]annulene

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, tsukubadiene-forming)

Comments: The synthesis of the diterpene tsukubadiene has been shown to occur in the Actinobacterium Streptomyces tsukubaensis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Yamada, Y., Arima, S., Nagamitsu, T., Johmoto, K., Uekusa, H., Eguchi, T., Shin-ya, K., Cane, D.E. and Ikeda, H. Novel terpenes generated by heterologous expression of bacterial terpene synthase genes in an engineered Streptomyces host. J. Antibiot. (Tokyo) 68 (2015) 385-394. [PMID: 25605043]

2. Rabe, P., Rinkel, J., Dolja, E., Schmitz, T., Nubbemeyer, B., Luu, T.H. and Dickschat, J.S. Mechanistic investigations of two bacterial diterpene cyclases: spiroviolene synthase and tsukubadiene synthase. Angew. Chem. Int. Ed. Engl. 56 (2017) 2776-2779. [PMID: 28146322]

[EC 4.2.3.159 created 2017]

EC 4.2.3.160

Accepted name: (2S,3R,6S,9S)-(–)-protoillud-7-ene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (2S,3R,6S,9S)-(–)-protoillud-7-ene + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: (2S,3R,6S,9S)-(–)-protoillud-7-ene = (2aS,4aS,7aS,7bR)-3,6,6,7b-tetramethyl-2,2a,4a,5,6,7,7a,7b-octahydro-1H-cyclobuta[e]indene
pentalenene = (3aS,5aS,8aR)-1,4,7,7-tetramethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene

Other name(s): TPS6 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (2S,3R,6S,9S)-(–)-protoillud-7-ene-forming]

Comments: The enzyme has been described from the slime-mould Dictyostelium discoideum. It is specific for (2E,6E)-farnesyl diphosphate. While the major product is the sequiterpene (2S,3R,6S,9S)-(–)-protoillud-7-ene, traces of pentalenene are also formed.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Chen, X., Kollner, T.G., Jia, Q., Norris, A., Santhanam, B., Rabe, P., Dickschat, J.S., Shaulsky, G., Gershenzon, J. and Chen, F. Terpene synthase genes in eukaryotes beyond plants and fungi: occurrence in social amoebae. Proc. Natl Acad. Sci. USA 113 (2016) 12132-12137. [PMID: 27790999]

2. Rabe, P., Rinkel, J., Nubbemeyer, B., Kollner, T.G., Chen, F. and Dickschat, J.S. Terpene cyclases from social Amoebae. Angew. Chem. Int. Ed. Engl. 55 (2016) 15420-15423. [PMID: 27862766]

[EC 4.2.3.160 created 2017]

EC 4.2.3.161

= Accepted name: (3S)-(+)-asterisca-2(9),6-diene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (3S)-(+)-asterisca-2(9),6-diene + diphosphate

For diagram of reaction click here

Glossary: (3S)-(+)-asterisca-2(9),6-diene = (4S,7Z)-2,2,4,7-tetramethyl-2,3,4,5,6,9-hexahydro-1H-cyclopenta[8]annulene

Other name(s): TPS2 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (3S)-(+)-asterisca-2(9),6-diene-forming]

Comments: The sequiterpene (3S)-(+)-asterisca-2(9),6-diene has been shown to be synthezised in the slime-mould Dictyostelium discoideum. The enzyme is specific for (2E,6E)-farnesyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Chen, X., Kollner, T.G., Jia, Q., Norris, A., Santhanam, B., Rabe, P., Dickschat, J.S., Shaulsky, G., Gershenzon, J. and Chen, F. Terpene synthase genes in eukaryotes beyond plants and fungi: occurrence in social amoebae. Proc. Natl Acad. Sci. USA 113 (2016) 12132-12137. [PMID: 27790999]

2. Rabe, P., Rinkel, J., Nubbemeyer, B., Kollner, T.G., Chen, F. and Dickschat, J.S. Terpene cyclases from social Amoebae. Angew. Chem. Int. Ed. Engl. 55 (2016) 15420-15423. [PMID: 27862766]

[EC 4.2.3.161 created 2017]

EC 4.2.3.162

Accepted name: (–)-α-amorphene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (–)-α-amorphene + diphosphate

For diagram of reaction click here

Glossary: (–)-α-amorphene = (1S,4aR,8aS)-4,7-dimethyl-1-(propan-2-yl)-1,2,4a,5,6,8a-hexahydronaphthalene

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (–)-α-amorphene-forming]

Comments: The enzyme, found in the bacterium Streptomyces viridochromogenes, is specific for (2E,6E)-farnesyl diphosphate and produces only (–)-α-amorphene.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P. and Dickschat, J.S. Rapid chemical characterization of bacterial terpene synthases. Angew. Chem. Int. Ed. Engl. 52 (2013) 1810-1812. [PMID: 23307484]

2. Rinkel, J., Rabe, P., Garbeva, P. and Dickschat, J.S. Lessons from 1,3-hydride shifts in sesquiterpene cyclizations. Angew. Chem. Int. Ed. Engl. 55 (2016) 13593-13596. [PMID: 27666571]

3. Rabe, P., Schmitz, T. and Dickschat, J.S. Mechanistic investigations on six bacterial terpene cyclases. Beilstein J. Org. Chem. 12 (2016) 1839-1850. [PMID: 27829890]

[EC 4.2.3.162 created 2017]

EC 4.2.3.163

Accepted name: (+)-corvol ether B synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-corvol ether B + diphosphate

For diagram of reaction click here

Glossary: (+)-corvol ether B = (1S,3R,5aR,6S,8aR)-3,6-dimethyl-1-(propan-2-yl)hexahydro-1H,3H-3,8a-methanocyclopenta[c]oxepine

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-corvol ether B-forming]

Comments: The enzyme, which forms the sesquiterpene (+)-corvol ether B, has been reported from the bacterium Kitasatospora setae.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Pahirulzaman, K.A. and Dickschat, J.S. Structures and biosynthesis of corvol ethers —sesquiterpenes from the actinomycete Kitasatospora setae. Angew. Chem. Int. Ed. Engl. 54 (2015) 6041-6045. [PMID: 25809275]

2. Rabe, P., Janusko, A., Goldfuss, B. and Dickschat, J.S. Experimental and theoretical studies on corvol ether biosynthesis. Chembiochem. 17 (2016) 146-149. [PMID: 26635093]

3. Rinkel, J., Rabe, P., Garbeva, P. and Dickschat, J.S. Lessons from 1,3-hydride shifts in sesquiterpene cyclizations. Angew. Chem. Int. Ed. Engl. 55 (2016) 13593-13596. [PMID: 27666571]

[EC 4.2.3.163 created 2017]

EC 4.2.3.164

Accepted name: (+)-eremophilene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (+)-eremophilene + diphosphate

For diagram of reaction click here

Glossary: (+)-eremophilene = (3S,4aS,5R)-4a,5-dimethyl-3-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,7-octahydronaphthalene

Other name(s): STC3 (gene name); geoA (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-eremophilene-forming]

Comments: The enzyme has been identified in the myxobacterium Sorangium cellulosum and in the fungus Fusarium fujikuroi.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Schifrin, A., Ly, T.T., Gunnewich, N., Zapp, J., Thiel, V., Schulz, S., Hannemann, F., Khatri, Y. and Bernhardt, R. Characterization of the gene cluster CYP264B1-geoA from Sorangium cellulosum So ce56: biosynthesis of (+)-eremophilene and its hydroxylation. Chembiochem 16 (2015) 337-344. [PMID: 25504914]

2. Burkhardt, I., Siemon, T., Henrot, M., Studt, L., Rosler, S., Tudzynski, B., Christmann, M. and Dickschat, J.S. Mechanistic characterisation of two sesquiterpene cyclases from the plant pathogenic fungus Fusarium fujikuroi. Angew. Chem. Int. Ed. Engl. 55 (2016) 8748-8751. [PMID: 27294564]

[EC 4.2.3.164 created 2017]

EC 4.2.3.165

Accepted name: (1R,4R,5S)-(–)-guaia-6,10(14)-diene synthase

Reaction: (2E,6E)-farnesyl diphosphate = (1R,4R,5S)-(–)-guaia-6,10(14)-diene + diphosphate

For diagram of reaction click here

Glossary: (1R,4R,5S)-(–)-guaia-6,10(14)-diene = (1R)-1-methyl-4-methylidene-7-(propan-2-yl)-1,2,3,3a,4,5,6,8a-octahydroazulene = (1R)-7-isopropyl-1-methyl-4-methylene-1,2,3,3a,4,5,6,8a-octahydroazulene

Other name(s): STC5 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (1R,4R,5S)-(–)-guaia-6,10(14)-diene-forming]

Comments: The original enzyme (STC5) from the fungus Fusarium fujikuroi is inactive because of a critically naturally occuring mutation that leads to an asparagine to lysine exchange in the NSE (Asn-Ser-Glu) triad, a highly conserved motif of type I terpene cyclases. Sequence correction by site-directed mutagenesis (K288N) restores activity.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Burkhardt, I., Siemon, T., Henrot, M., Studt, L., Rosler, S., Tudzynski, B., Christmann, M. and Dickschat, J.S. Mechanistic characterisation of two sesquiterpene cyclases from the plant pathogenic fungus Fusarium fujikuroi. Angew. Chem. Int. Ed. Engl. 55 (2016) 8748-8751. [PMID: 27294564]

[EC 4.2.3.165 created 2017]

EC 4.2.3.166

Accepted name: (+)-(1E,4E,6S,7R)-germacra-1(10),4-dien-6-ol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-(1E,4E,6S,7R)-germacra-1(10),4-dien-6-ol + diphosphate

For diagram of reaction click here

Glossary: (+)-(1E,4E,6S,7R)-germacra-1(10),4-dien-6-ol = (1S,2E,6E,10R)-3,7-dimethyl-10-(propan-2-yl)cyclodeca-2,6-dien-1-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-(1E,4E,6S,7R)-germacra-1(10),4-dien-6-ol-forming]

Comments: The enzyme has been identified in the bacterium Streptomyces pratensis. It is specific for (2E,6E)-farnesyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Barra, L., Rinkel, J., Riclea, R., Citron, C.A., Klapschinski, T.A., Janusko, A. and Dickschat, J.S. Conformational analysis, thermal rearrangement, and EI-MS fragmentation mechanism of ((1(10)E,4E,6S,7R)-germacradien-6-ol by 13C-labeling experiments. Angew. Chem. Int. Ed. Engl. 54 (2015) 13448-13451. [PMID: 26361082]

[EC 4.2.3.166 created 2017]

EC 4.2.3.167

Accepted name: dolabella-3,7-dien-18-ol synthase

Reaction: geranylgeranyl diphosphate + H2O = (3E,7E)-dolabella-3,7-dien-18-ol + diphosphate

For diagram of reaction click here

Glossary: (3E,7E)-dolabella-3,7-dien-18-ol = 2-[(1R,3aR,5E,9E,12aR)-3a,6,10-trimethyl-1,2,3,3a,4,7,8,11,12,12a-decahydrocyclopenta[11]annulen-1-yl]propan-2-ol

Other name(s): TPS20 (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [cyclizing, (3E,7E)-dolabella-3,7-dien-18-ol-forming]

Comments: Isolated from an ecotype of the plant Arabidopsis thaliana from Cape Verde Islands. The enzyme also gives (3E,7E)-dolathalia-3,7,11-triene and traces of other terpenoids. cf. EC 4.2.3.168 dolathalia-3,7,11-triene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Wang, Q., Jia, M., Huh, J.H., Muchlinski, A., Peters, R.J. and Tholl, D. Identification of a dolabellane type diterpene synthase and other root-expressed diterpene synthases in Arabidopsis. Front. Plant Sci. 7 (2016) 1761. [PMID: 27933080]

[EC 4.2.3.167 created 2017]

EC 4.2.3.168

Accepted name: dolathalia-3,7,11-triene synthase

Reaction: geranylgeranyl diphosphate = (3E,7E)-dolathalia-3,7,11-triene + diphosphate

For diagram of reaction click here

Glossary: (3E,7E)-dolathalia-3,7,11-triene = (7E,11E)-3,3,7,11,13a-pentamethy1-2,3,5,6,9,10,13,13a-octahydro-1H-benzo[11]annulene

Other name(s): TPS20 (gene name)

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [cyclizing, (3E,7E)-dolathalia-3,7,11-triene-forming]

Comments: Isolated from an ecotype of the plant Arabidopsis thaliana from Cape Verde Islands. The enzyme also gives (3E,7E)-dolabella-3,7-dien-18-ol and traces of other terpenoids. cf. EC 4.2.3.167 dolabella-3,7-dien-18-ol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Wang, Q., Jia, M., Huh, J.H., Muchlinski, A., Peters, R.J. and Tholl, D. Identification of a dolabellane type diterpene synthase and other root-expressed diterpene synthases in Arabidopsis. Front. Plant Sci. 7 (2016) 1761. [PMID: 27933080]

[EC 4.2.3.168 created 2017]

EC 4.2.3.169

Accepted name: 7-epi-α-eudesmol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = 7-epi-α-eudesmol + diphosphate

For diagram of reaction click here

Glossary: 7-epi-α-eudesmol = 2-[(2S,4aR,8aR)-4a,8-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-2-yl]propan-2-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 7-epi-α-eudesmol-forming)

Comments: The enzyme, found in the bacterium Streptomyces viridochromogenes, is specific for (2E,6E)-farnesyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Schmitz, T. and Dickschat, J.S. Mechanistic investigations on six bacterial terpene cyclases. Beilstein J. Org. Chem. 12 (2016) 1839-1850. [PMID: 27829890]

[EC 4.2.3.169 created 2017]

EC 4.2.3.170

Accepted name: 4-epi-cubebol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = 4-epi-cubebol + diphosphate

For diagram of reaction click here

Glossary: 4-epi-cubebol = (3S,3aS,3bR,4S,7S,7aS)-4-(2-hydroxypropan-2-yl)-7-methyloctahydro-1H-cyclopenta[1,3]cyclopropa[1,2]benzen-3-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 4-epi-cubebol-forming)

Comments: The enzyme, found in the bacterium Streptosporangium roseum, is specific for (2E,6E)-farnesyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Schmitz, T. and Dickschat, J.S. Mechanistic investigations on six bacterial terpene cyclases. Beilstein J. Org. Chem. 12 (2016) 1839-1850. [PMID: 27829890]

[EC 4.2.3.170 created 2017]

EC 4.2.3.171

Accepted name: (+)-corvol ether A synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-corvol ether A + diphosphate

For diagram of reaction click here

Glossary: (+)-corvol ether A = (1R,4S,4aR,7R,8aR)-4,7-dimethyl-1-(propan-2-yl)decahydro-1,7-epoxynaphthalene

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-corvol ether A-forming]

Comments: The enzyme, which forms the sesquiterpene (+)-corvol ether A, has been reported from the bacterium Kitasatospora setae.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P., Pahirulzaman, K.A. and Dickschat, J.S. Structures and biosynthesis of corvol ethers —sesquiterpenes from the actinomycete Kitasatospora setae. Angew. Chem. Int. Ed. Engl. 54 (2015) 6041-6045. [PMID: 25809275]

2. Rabe, P., Janusko, A., Goldfuss, B. and Dickschat, J.S. Experimental and theoretical studies on corvol ether biosynthesis. Chembiochem. 17 (2016) 146-149. [PMID: 26635093]

3. Rinkel, J., Rabe, P., Garbeva, P. and Dickschat, J.S. Lessons from 1,3-hydride shifts in sesquiterpene cyclizations. Angew. Chem. Int. Ed. Engl. 55 (2016) 13593-13596. [PMID: 27666571]

[EC 4.2.3.171 created 2017]

EC 4.2.3.172

Accepted name: 10-epi-juneol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = 10-epi-juneol + diphosphate

For diagram of reaction click here

Glossary: 10-epi-juneol = 10α-eudesm-4(14)-en-6α-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 10-epi-juneol-forming)

Comments: Isolated from the plant Inula hupehensis. The enzyme also gives gives τ-cadinol and traces of other terpenoids, see EC 4.2.3.173, τ-cadinol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gou, J.B., Li, Z.Q., Li, C.F., Chen, F.F., Lv, S.Y. and Zhang, Y.S. Molecular cloning and functional analysis of a 10-epi-junenol synthase from Inula hupehensis. Plant Physiol. Biochem. 106 (2016) 288-294. [PMID: 27231873]

[EC 4.2.3.172 created 2017]

EC 4.2.3.173

Accepted name: τ-cadinol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = τ-cadinol + diphosphate

For diagram of reaction click here

Glossary: τ-cadinol = 10β-cadin-4-en-10-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, τ-cadinol-forming)

Comments: Isolated from the plant Inula hupehensis. The enzyme also gives 10-epi-juneol and traces of other terpenoids, see EC 4.2.3.172, 10-epi-juneol synthase. It has also been isolated from the plants maize (Zea mays) and lavender (Lavandula angustifolia).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gou, J.B., Li, Z.Q., Li, C.F., Chen, F.F., Lv, S.Y. and Zhang, Y.S. Molecular cloning and functional analysis of a 10-epi-junenol synthase from Inula hupehensis. Plant Physiol. Biochem. 106 (2016) 288-294. [PMID: 27231873]

2. Jullien, F., Moja, S., Bony, A., Legrand, S., Petit, C., Benabdelkader, T., Poirot, K., Fiorucci, S., Guitton, Y., Nicole, F., Baudino, S. and Magnard, J.L. Isolation and functional characterization of a τ-cadinol synthase, a new sesquiterpene synthase from Lavandula angustifolia. Plant Mol. Biol. 84 (2014) 227-241. [PMID: 24078339]

3. Ren, F., Mao, H., Liang, J., Liu, J., Shu, K. and Wang, Q. Functional characterization of ZmTPS7 reveals a maize τ-cadinol synthase involved in stress response. Planta 244 (2016) 1065-1074. [PMID: 27421723]

[EC 4.2.3.173 created 2017]

EC 4.2.3.174

Accepted name: (2E,6E)-hedycaryol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-hedycaryol + diphosphate

For diagram of reaction click here

Glossary: (2E,6E)-hedycaryol = (1E,4E,7S)-germacra-1(10),4-dien-11-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (2E,6E)-hedycaryol-forming]

Comments: Isolated from the plant Camellia brevistyla. See also EC 4.2.3.187, (2Z,6E)-hedycaryol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Hattan, J., Shindo, K., Ito, T., Shibuya, Y., Watanabe, A., Tagaki, C., Ohno, F., Sasaki, T., Ishii, J., Kondo, A. and Misawa, N. Identification of a novel hedycaryol synthase gene isolated from Camellia brevistyla flowers and floral scent of Camellia cultivars. Planta 243 (2016) 959-972. [PMID: 26744017]

[EC 4.2.3.174 created 2017]

EC 4.2.3.175

Accepted name: 10-epi-cubebol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = 10-epi-cubebol + diphosphate

For diagram of reaction click here

Other name(s): sce6369

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 10-epi-cubebol-forming)

Comments: Isolated from the bacterium Sorangium cellulosum So ce56. The enzyme is also responsible for the formation of trace amounts of many other sesquiterpenes, mainly cadinanes and cubebanes.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Schifrin, A., Khatri, Y., Kirsch, P., Thiel, V., Schulz, S. and Bernhardt, R. A single terpene synthase is responsible for a wide variety of sesquiterpenes in Sorangium cellulosum Soce56. Org. Biomol. Chem. 14 (2016) 3385-3393. [PMID: 26947062]

[EC 4.2.3.175 created 2017]

EC 4.2.3.176

Accepted name: sesterfisherol synthase

Reaction: (2E,6E,10E,14E)-geranylfarnesyl diphosphate + H2O = sesterfisherol + diphosphate

For diagram of reaction click here Glossary: sesterfisherol = (3R,3aS,6S,6aR,7aR,10R,10aS,11aR)-3,6,7a,12-tetramethyl-10-(propan-2-yl)-2,3,3a,4,5,6,6a,7,7a,8,9,10,10a,11-tetradecahydrocyclopenta[4,5]cycloocta[f]inden-11a(1H)-ol

Other name(s): NfSS

Systematic name: (2E,6E,10E,14E)-geranylfarnesyl-diphosphate diphosphate-lyase (cyclizing, sesterfisherol-forming)

Comments: Isolated from the fungus Neosartorya fischeri.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Ye, Y., Minami, A., Mandi, A., Liu, C., Taniguchi, T., Kuzuyama, T., Monde, K., Gomi, K. and Oikawa, H. Genome mining for sesterterpenes using bifunctional terpene synthases reveals a unified intermediate of di/sesterterpenes. J. Am. Chem. Soc. 137 (2015) 11846-11853. [PMID: 26332841]

[EC 4.2.3.176 created 2017]

EC 4.2.3.177

Accepted name: β-thujene synthase

Reaction: geranyl diphosphate = β-thujene + diphosphate

For diagram of reaction click here

Other name(s): CoTPS1

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, β-thujene-forming)

Comments: Isolated from the plant Cananga odorata var. fruticosa (ylang ylang). The enzyme forms roughly equal proportions of β-thujene, sabinene, β-pinene and α-terpinene see EC 4.2.3.109/EC 4.2.3.110 sabinene synthase, EC 4.2.3.120/EC 4.2.3.122 β-pinene synthase, EC 4.2.3.115 α-terpinene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Jin, J., Kim, M.J., Dhandapani, S., Tjhang, J.G., Yin, J.L., Wong, L., Sarojam, R., Chua, N.H. and Jang, I.C. The floral transcriptome of ylang ylang (Cananga odorata var. fruticosa) uncovers biosynthetic pathways for volatile organic compounds and a multifunctional and novel sesquiterpene synthase. J. Exp. Bot. 66 (2015) 3959-3975. [PMID: 25956881]

[EC 4.2.3.177 created 2017]

EC 4.2.3.178

Accepted name: stellata-2,6,19-triene synthase

Reaction: (2E,6E,10E,14E)-geranylfarnesyl diphosphate = stellata-2,6,19-triene + diphosphate

For diagram of reaction click here Glossary: stellata-2,6,19-triene = (3S,3aR,5aR,7E,11E,14aR,14bR)-5a,8,12,14b-tetramethyl-3-(prop-1-en-2-yl)-1,2,3,3a,4,5,5a,6,9,10,13,14,14a,14b-tetradecahydrocycloundeca[e]indene

Systematic name: (2E,6E,10E,14E)-geranylfarnesyl-diphosphate diphosphate-lyase (cylizing, stellata-2,6,19-triene-forming)

Comments: Isolated from the fungus Aspergillus stellatus.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Matsuda, Y., Mitsuhashi, T., Quan, Z. and Abe, I. Molecular basis for stellatic acid biosynthesis: a genome mining approach for discovery of sesterterpene synthases. Org. Lett. 17 (2015) 4644-4647. [PMID: 26351860]

[EC 4.2.3.178 created 2017]

EC 4.2.3.179

Accepted name: guaia-4,6-diene synthase

Reaction: (2E,6E)-farnesyl diphosphate = guaia-4,6-diene + diphosphate

For diagram of reaction click here

Other name(s): XsTPS2

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, guaia-4,6-diene-forming)

Comments: Isolated from the plant Xanthium strumarium (rough cocklebur).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Li, Y., Chen, F., Li, Z., Li, C. and Zhang, Y. Identification and functional characterization of sesquiterpene synthases from Xanthium strumarium. Plant Cell Physiol 57 (2016) 630-641. [PMID: 26858282]

[EC 4.2.3.179 created 2017]

EC 4.2.3.180

Accepted name: pseudolaratriene synthase

Reaction: geranylgeranyl diphosphate = pseudolaratriene + diphosphate

For diagram of reaction click here

Glossary: pseudolaradiene = (1RS,3aSR,8aRS)-3a,6-dimethyl-1-(6-methylhepta-2,5-dien-2-yl)-1,2,3,3a,4,7,8,8a-octahydrohydroazulene

Other name(s): PxaTPS8

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, pseudolaradiene-forming)

Comments: Isolated from the plant Pseudolarix amabilis (golden larch). The product is oxidized to pseudolaric acid B, a microtubule-destabilizing agent.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mafu, S., Karunanithi, P.S., Palazzo, T.A., Harrod, B.L., Rodriguez, S.M., Mollhoff, I.N., O'Brien, T.E., Tong, S., Fiehn, O., Tantillo, D.J., Bohlmann, J. and Zerbe, P. Biosynthesis of the microtubule-destabilizing diterpene pseudolaric acid B from golden larch involves an unusual diterpene synthase. Proc. Natl Acad. Sci. USA 114 (2017) 974-979. [PMID: 28096378]

[EC 4.2.3.180 created 2017]

EC 4.2.3.181

Accepted name: selina-4(15),7(11)-diene synthase

Reaction: (2E,6E)-farnesyl diphosphate = selina-4(15),7(11)-diene + diphosphate

For diagram of reaction click here

Other name(s): SdS

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, selina-4(15),7(11)-diene-forming)

Comments: Isolated from the bacteria Streptomyces pristinaespiralis and S. somaliensis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rabe, P. and Dickschat, J.S. Rapid chemical characterization of bacterial terpene synthases. Angew. Chem. Int. Ed. Engl. 52 (2013) 1810-1812. [PMID: 23307484]

2. Baer, P., Rabe, P., Fischer, K., Citron, C.A., Klapschinski, T.A., Groll, M. and Dickschat, J.S. Induced-fit mechanism in class I terpene cyclases. Angew. Chem. Int. Ed. Engl. 53 (2014) 7652-7656. [PMID: 24890698]

[EC 4.2.3.181 created 2017]

EC 4.2.3.182

Accepted name: pristinol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-(2S,3R,9R)-pristinol + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: (+)-(2S,3R,9R)-pristinol = (1R,6R,9aS)-1,4,8,8-tetramethyl-2,3,5,6,7,8,9,9a-octahydro-1H-cyclopenta[8]annulen-6-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-(2S,3R,9R)-pristinol-forming]

Comments: Isolated from the bacterium Streptomyces pristinaespiralis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Klapschinski, T.A., Rabe, P. and Dickschat, J.S. Pristinol, a sesquiterpene alcohol with an unusual skeleton from Streptomyces pristinaespiralis. Angew. Chem. Int. Ed. Engl. 55 (2016) 10141-10144. [PMID: 27403888]

[EC 4.2.3.182 created 2017]

EC 4.2.3.183

Accepted name: nezukol synthase

Reaction: (+)-copalyl diphosphate + H2O = nezukol + diphosphate

For diagram of reaction click here

Glossary: (+)-copalyl diphosphate = (2E)-3-methyl-5-[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidenedecahydronaphthalen-1-yl]pent-2-en-1-yl trihydrogen diphosphate
nezukol = pimar-15-en-8-ol

Other name(s): TPS2

Systematic name: (+)-copalyl-diphosphate diphosphate-lyase (cyclizing, nezukol-forming)

Comments: Isolated from the plant Isodon rubescens.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Pelot, K.A., Hagelthorn, D.M., Addison, J.B. and Zerbe, P. Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases. PLoS One 12 (2017) e0176507. [PMID: 28445526]

[EC 4.2.3.183 created 2017]

EC 4.2.3.184

Accepted name: 5-hydroxy-α-gurjunene synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = 5-hydroxy-α-gurjunene + diphosphate

For diagram of reaction click here

Other name(s): MpMTPSL4

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 5-hydroxy-α-gurjunene-forming)

Comments: Isolated from the liverwort Marchantia polymorpha.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Kumar, S., Kempinski, C., Zhuang, X., Norris, A., Mafu, S., Zi, J., Bell, S.A., Nybo, S.E., Kinison, S.E., Jiang, Z., Goklany, S., Linscott, K.B., Chen, X., Jia, Q., Brown, S.D., Bowman, J.L., Babbitt, P.C., Peters, R.J., Chen, F. and Chappell, J. Molecular diversity of terpene synthases in the liverwort Marchantia polymorpha. Plant Cell 28 (2016) 2632-2650. [PMID: 27650333]

[EC 4.2.3.184 created 2017]

EC 4.2.3.185

Accepted name: ent-atiserene synthase

Reaction: ent-copalyl diphosphate = ent-atiserene + diphosphate

For diagram of reaction click here and mechanism click here

Other name(s): IrKSL4

Systematic name: ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-atiserine-forming)

Comments: Isolated from the plant Isodon rubescens.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Jin, B., Cui, G., Guo, J., Tang, J., Duan, L., Lin, H., Shen, Y., Chen, T., Zhang, H. and Huang, L. Functional diversification of kaurene synthase-like genes in Isodon rubescens. Plant Physiol. 174 (2017) 943-955. [PMID: 28381502]

[EC 4.2.3.185 created 2017]

EC 4.2.3.186

Accepted name: ent-13-epi-manoyl oxide synthase

Reaction: ent-8α-hydroxylabd-13-en-15-yl diphosphate = ent-13-epi-manoyl oxide + diphosphate

For diagram of reaction click here

Glossary: Ent-13-epi-manoyl oxide = (13R)-ent-8,13-epoxylabd-14-ene

Other name(s): SmKSL2; ent-LDPP synthase

Systematic name: ent-8α-hydroxylabd-13-en-15-yl-diphosphate diphosphate-lyase (cyclizing, ent-13-epi-manoyl-oxide-forming)

Comments: Isolated from the plant Salvia miltiorrhiza (red sage).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Cui, G., Duan, L., Jin, B., Qian, J., Xue, Z., Shen, G., Snyder, J.H., Song, J., Chen, S., Huang, L., Peters, R.J. and Qi, X. Functional divergence of diterpene syntheses in the medicinal plant Salvia miltiorrhiza. Plant Physiol. 169 (2015) 1607-1618. [PMID: 26077765]

[EC 4.2.3.186 created 2017]

EC 4.2.3.187

Accepted name: (2Z,6E)-hedycaryol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (2Z,6E)-hedycaryol + diphosphate

For diagram of reaction click here

Glossary: (2Z,6E)-hedycaryol = (1E,4Z,7S)-germacra-1(10),4-dien-11-ol

Other name(s): HcS

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (2Z,6E)-hedycaryol-forming]

Comments: Isolated from the bacterium Kitasatospora setae. The stereochemistry suggests the farnesyl diphosphate rearranges to nerolidyl diphosphate or an equivalent intermediate before cyclization. See also EC 4.2.3.174 (2E,6E)-hedycaryol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Baer, P., Rabe, P., Citron, C.A., de Oliveira Mann, C.C., Kaufmann, N., Groll, M. and Dickschat, J.S. Hedycaryol synthase in complex with nerolidol reveals terpene cyclase mechanism. Chembiochem 15 (2014) 213-216. [PMID: 24399794]

[EC 4.2.3.187 created 2017]

EC 4.2.3.188

Accepted name: β-geranylfarnesene synthase

Reaction: (1) all-trans-geranylfarnesyl diphosphate = β-geranylfarnesene + diphosphate
(2) all-trans-hexaprenyl diphosphate = β-hexaprene + diphosphate
(3) all-trans-heptaprenyl diphosphate = β-heptaprene + diphosphate

For diagram of reaction click here or click here.

Glossary: β-geranylfarnesene = (6E,10E,14E)-7,11,15,19-tetramethyl-3-methyleneicosa-1,6,10,14,18-pentaene

Other name(s): Bcl-TS

Systematic name: all-trans-geranylfarnesyl-diphosphate diphosphate-lyase (β-geranylfarnesene-forming)

Comments: Isolated from the bacterium Bacillus clausii. The enzyme acts on a range of polyprenyl diphosphates.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Sato, T., Yamaga, H., Kashima, S., Murata, Y., Shinada, T., Nakano, C. and Hoshino, T. Identification of novel sesterterpene/triterpene synthase from Bacillus clausii. Chembiochem 14 (2013) 822-825. [PMID: 23554321]

2. Ueda, D., Yamaga, H., Murakami, M., Totsuka, Y., Shinada, T. and Sato, T. Biosynthesis of sesterterpenes, head-to-tail triterpenes, and sesquarterpenes in Bacillus clausii: identification of multifunctional enzymes and analysis of isoprenoid metabolites. Chembiochem 16 (2015) 1371-1377. [PMID: 25882275]

[EC 4.2.3.188 created 2017]

EC 4.2.3.189

Accepted name: 9,13-epoxylabda-14-ene synthase

Reaction: peregrinol diphosphate = (13ξ)-9,13-epoxylabda-14-ene + diphosphate

For diagram of reaction click here

Glossary: peregrinol diphosphate = (13E)-9-hydroxy-8α-labda-13-en-15-yl diphosphate

Other name(s): MvELS

Systematic name: peregrinol-diphosphate diphosphate-lyase (9,13-epoxylabda-14-ene-forming)

Comments: Isolated from the plant Marrubium vulgare (white horehound). Involved in marrubiin biosynthesis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Zerbe, P., Chiang, A., Dullat, H., O'Neil-Johnson, M., Starks, C., Hamberger, B. and Bohlmann, J. Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare. Plant J. 79 (2014) 914-927. [PMID: 24990389]

[EC 4.2.3.189 created 2017]

EC 4.2.3.190

Accepted name: manoyl oxide synthase

Reaction: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate = manoyl oxide + diphosphate

For diagram of reaction click here

Glossary: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate = 8-hydroxycopalyl diphosphate
manoyl oxide = (13R)-8,13-epoxylabd-14-ene

Other name(s): GrTPS6; CfTPS3; CfTPS4; MvELS

Systematic name: (13E)-8α-hydroxylabd-13-en-15-yl-diphosphate diphosphate-lyase (manoyl-oxide-forming)

Comments: Manoyl oxide is found in many plants. This enzyme has been isolated from the plants, Grindelia hirsutula (gum weed), Plectranthus barbatus (forskohlii) and Marrubium vulgare (white horehound).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Zerbe, P., Hamberger, B., Yuen, M.M., Chiang, A., Sandhu, H.K., Madilao, L.L., Nguyen, A., Hamberger, B., Bach, S.S. and Bohlmann, J. Gene discovery of modular diterpene metabolism in nonmodel systems. Plant Physiol. 162 (2013) 1073-1091. [PMID: 23613273]

2. Pateraki, I., Andersen-Ranberg, J., Hamberger, B., Heskes, A.M., Martens, H.J., Zerbe, P., Bach, S.S., Moller, B.L., Bohlmann, J. and Hamberger, B. Manoyl oxide (13R), the biosynthetic precursor of forskolin, is synthesized in specialized root cork cells in Coleus forskohlii. Plant Physiol. 164 (2014) 1222-1236. [PMID: 24481136]

3. Zerbe, P., Chiang, A., Dullat, H., O'Neil-Johnson, M., Starks, C., Hamberger, B. and Bohlmann, J. Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare. Plant J. 79 (2014) 914-927. [PMID: 24990389]

[EC 4.2.3.190 created 2017]

EC 4.2.3.191

Accepted name: cycloaraneosene synthase

Reaction: geranylgeranyl diphosphate = cycloaraneosene + diphosphate

For diagram of reaction click here

Glossary: cycloaraneosene = (1R,3aR,9aS,10aR)-1,9a-dimethyl-4-methylene-7-(propan-2-yl)-1,2,3,3a,4,5,6,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene

Other name(s): SdnA

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cycloaraneosene-forming)

Comments: Isolated from the fungus Sordaria araneosa. Cycloaraneosene is a precursor of the antibiotic sordarin.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Kudo, F., Matsuura, Y., Hayashi, T., Fukushima, M. and Eguchi, T. Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase. J. Antibiot. (Tokyo) 69 (2016) 541-548. [PMID: 27072286]

[EC 4.2.3.191 created 2017]

EC 4.2.3.192

Accepted name: labda-7,13(16),14-triene synthase

Reaction: (13E)-labda-7,13-dienyl diphosphate = labda-7,13(16),14-triene + diphosphate

For diagram of reaction click here

Other name(s): SCLAV_p0491

Systematic name: (13E)-labda-7,13-dienyl-diphosphate diphosphate-lyase (labda-7,13(16),14-triene-forming)

Comments: Isolated from the bacterium Streptomyces clavuligerus.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Yamada, Y., Komatsu, M. and Ikeda, H. Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms. J. Antibiot. (Tokyo) 69 (2016) 515-523. [PMID: 26814669]

[EC 4.2.3.192 created 2017]

EC 4.2.3.193

Accepted name: (12E)-labda-8(17),12,14-triene synthase

Reaction: (+)-copalyl diphosphate = (12E)-labda-8(17),12,14-triene + diphosphate

For diagram of reaction click here

Other name(s): CldD

Systematic name: (+)-copalyl-diphosphate diphosphate-lyase [(12E)-labda-8(17),12,14-triene-forming]

Comments: Isolated from the bacterium Streptomyces cyslabdanicus.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Yamada, Y., Komatsu, M. and Ikeda, H. Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms. J. Antibiot. (Tokyo) 69 (2016) 515-523. [PMID: 26814669]

[EC 4.2.3.193 created 2017]

EC 4.2.3.194

Accepted name: (–)-drimenol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H2O = (–)-drimenol + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: (–)-drimenol = drim-7-en-11-ol

Other name(s): PhDS; VoTPS3; farnesyl pyrophosphate:drimenol cyclase; drimenol cyclase; (2E,6E)-farnesyl-diphosphate diphosphohydrolase (drimenol-forming)

Systematic name: (2E,6E)-farnesyl-diphosphate diphospho-lyase [cyclising, (–)-drimenol-forming]

Comments: Isolated from the plants Valeriana officinalis (valerian) and Persicaria hydropiper (water pepper). The enzyme does not act on farnesol or drimenol diphosphate. Using 18-oxygen labelled water 18-oxygen was incorporated suggesting involvement of a stabilised carbocation or an equivalent species.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Banthorp, D.V., Brown, J.T. and Morris, G.S. Partial purification of farnesyl pyrophosphate:drimenol cyclase and geranylgerany pyrophosphate:sclareol cyclase, using cell culture as a source of material. Phytochemistry 31 (1992) 3391-3395.

2. Kwon, M., Cochrane, S.A., Vederas, J.C. and Ro, D.K. Molecular cloning and characterization of drimenol synthase from valerian plant (Valeriana officinalis). FEBS Lett. 588 (2014) 4597-4603. [PMID: 25447532]

3. Henquet, M.GL., Prota, N., van der Hooft, J.JJ., Varbanova-Herde, M., Hulzink, R.JM., de Vos, M., Prins, M., de Both, M.TJ., Franssen, M.CR., Bouwmeester, H. and Jongsma, M. Identification of a drimenol synthase and drimenol oxidase from Persicaria hydropiper, involved in the biosynthesis of insect deterrent drimanes. Plant J. 90 (2017) 1052-1063. [PMID: 28258968]

[EC 4.2.3.194 created 2011 as EC 3.1.7.7, transferred 2017 to EC 4.2.3.194]

EC 4.2.3.195

Accepted name: rhizathalene A synthase

Reaction: geranylgeranyl diphosphate = rhizathalene A + diphosphate

For diagram of reaction click here and mechanism click here

Other name(s): TPS08 (gene name)

Systematic name: geranygeranyl-diphosphate diphosphate-lyase (rhizathalene A-forming)

Comments: The enzyme was identified in the roots of the plant Arabidopsis thaliana (thale cress). The product is a semivolatile diterpene that acts as a local antifeedant in belowground direct defense against root-feeding insects.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Vaughan, M.M., Wang, Q., Webster, F.X., Kiemle, D., Hong, Y.J., Tantillo, D.J., Coates, R.M., Wray, A.T., Askew, W., O'Donnell, C., Tokuhisa, J.G. and Tholl, D. Formation of the unusual semivolatile diterpene rhizathalene by the Arabidopsis class I terpene synthase TPS08 in the root stele is involved in defense against belowground herbivory. Plant Cell 25 (2013) 1108-1125. [PMID: 23512856]

[EC 4.2.3.195 created 2017]

EC 4.2.3.196

Accepted name: dolabradiene synthase

Reaction: ent-copalyl diphosphate = dolabradiene + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: dolabradiene = (4aS,4bR,7S,8aR,10aS)-7-ethenyl-4b,7,10a-trimethyl-1-methylidene-decahydrophenanthrene

Other name(s): KSL4 (gene name)

Systematic name: ent-copalyl-diphosphate diphosphate-lyase (dolabradiene-forming)

Comments: The enzyme, which has been characterized from maize, is involved in the biosynthesis of dolabralexins (type of antifungal phytoalexins).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mafu, S., Ding, Y., Murphy, K.M., Yaacoobi, O., Addison, J.B., Wang, Q., Shen, Z., Briggs, S.P., Bohlmann, J., Castro-Falcon, G., Hughes, C.C., Betsiashvili, M., Huffaker, A., Schmelz, E.A. and Zerbe, P. Discovery, biosynthesis and stress-related accumulation of dolabradiene-derived defenses in maize. Plant Physiol. 176 (2018) 2677-2690. [PMID: 29475898]

[EC 4.2.3.196 created 2018]

EC 4.2.3.197

Accepted name: eudesmane-5,11-diol synthase

Reaction: (2E,6E)-farnesyl diphosphate + 2 H2O = 7-epi-ent-eudesmane-5,11-diol + diphosphate

For diagram of reaction click here and mechanism click here.

Glossary: 7-epi-ent-eudesmane-5,11-diol = (4S,4aS,6R,8aS)-6-(2-hydroxypropan-2-yl)-4,8a-dimethyldecahydronaphthalen-4a-ol

Other name(s): ZmEDS (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 7-epi-ent-eudesmane-5,11-diol-forming)

Comments: Isolated from the plant Zea mays (maize). The product is named in the reference using a different numbering scheme for eudesmane.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Liang, J., Liu, J., Brown, R., Jia, M., Zhou, K., Peters, R.J. and Wang, Q. Direct production of dihydroxylated sesquiterpenoids by a maize terpene synthase. Plant J. 94 (2018) 847-856. [PMID: 29570233]

[EC 4.2.3.197 created 2018]

EC 4.2.3.198

Accepted name: α-selinene synthase

Reaction: (2E,6E)-farnesyl diphosphate = α-selinene + diphosphate

For diagram of reaction click here

Glossary: α-selinene = (2R,4aR,8aS)-4,8a-dimethyl-2-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,8a-octahydronaphthalene
β-selinene = (4aR,7R,8aS)-4a-methyl-1-methylidene-7-(prop-1-en-2-yl)decahydronaphthalene
aromadendrene = (1aR,4aR,7R,7aR,7bS)-1,1,7-trimethyl-4-methylidenedecahydro-1H-cyclopropa[e]azulene

Other name(s): LfTPS2 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, α-selinene-forming)

Comments: The enzyme from the plant Ocimum basilicum (sweet basil) also produces β-selinene while that from Liquidambar formosana (Formosan sweet gum) also produces traces of aromadendrene.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Iijima, Y., Davidovich-Rikanati, R., Fridman, E., Gang, D.R., Bar, E., Lewinsohn, E. and Pichersky, E. The biochemical and molecular basis for the divergent patterns in the biosynthesis of terpenes and phenylpropenes in the peltate glands of three cultivars of basil. Plant Physiol. 136 (2004) 3724-3736. [PMID: 15516500]

2. Chuang, L., Wen, C.H., Lee, Y.R., Lin, Y.L., Hsu, L.R., Wang, S.Y. and Chu, F.H. Identification, functional characterization, and seasonal expression patterns of five sesquiterpene synthases in Liquidambar formosana. J Nat Prod 81 (2018) 1162-1172. [PMID: 29746128]

[EC 4.2.3.198 created 2018]

EC 4.2.3.199

Accepted name: (-)-5-epieremophilene synthase

Reaction: (2E,6E)-farnesyl-diphosphate = (-)-5-epieremophilene + diphosphate

For diagram of reaction click here

Glossary: (-)-5-epieremophilene = (3R,4aS,5S)-4a,5-dimethyl-3-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,7-octahydronaphthalene

Other name(s): STPS1 (gene name); STP2 (gene name); STP3 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (-)-epieremophilene-forming]

Comments: The plant Salvia miltiorrhiza (danshen) produces three different forms of the enzyme, encoded by paralogous genes, that exhibit different spacial expression patterns and respond differently to hormone treatment.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Fang, X., Li, C.Y., Yang, Y., Cui, M.Y., Chen, X.Y. and Yang, L. Identification of a novel (-)-5-epieremophilene synthase from Salvia miltiorrhiza via transcriptome mining. Front. Plant Sci. 8 (2017) 627. [PMID: 28487717]

[EC 4.2.3.199 created 2018]

EC 4.2.3.200

Accepted name: β-pinacene synthase

Reaction: geranylgeranyl diphosphate = β-pinacene + diphosphate

For diagram of reaction click here

Glossary: β-pinacene = 4,8,12-trimethyl-1-(propan-2-yl)cyclotetradeca-1,3,7,11-tetraene

Other name(s): PcS

Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, β-pinacene-forming)

Comments: Isolated from the slime mould Dictyostelium discoideum. The 1-proR hydrogen atom of geranylgeranyl diphosphate is lost in the reaction.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Rinkel, J., Rabe, P., Chen, X., Kollner, T.G., Chen, F. and Dickschat, J.S. Mechanisms of the diterpene cyclases β-pinacene synthase from Dictyostelium discoideum and hydropyrene synthase from Streptomyces clavuligerus. Chemistry 23 (2017) 10501-10505. [PMID: 28696553]

[EC 4.2.3.200 created 2018]


Continued with EC 4.2.99
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