Enzyme Nomenclature

Continued from EC 4.1.2

EC 4.1.3 and EC 4.1.99

Sections

EC 4.1.3 Oxo-Acid-Lyases
EC 4.1.99 Other Carbon-Carbon Lyases


EC 4.1.3 Oxo-Acid-Lyases

Contents

EC 4.1.3.1 isocitrate lyase
EC 4.1.3.2 now EC 2.3.3.9
EC 4.1.3.3 N-acetylneuraminate lyase
EC 4.1.3.4 hydroxymethylglutaryl-CoA lyase
EC 4.1.3.5 now EC 2.3.3.10
EC 4.1.3.6 [citrate (pro-3S)-lyase]
EC 4.1.3.7 now EC 2.3.3.1
EC 4.1.3.8 now EC 2.3.3.8
EC 4.1.3.9 now EC 2.3.3.11
EC 4.1.3.10 now EC 2.3.3.7
EC 4.1.3.11 now EC 2.3.3.12
EC 4.1.3.12 now EC 2.3.3.13
EC 4.1.3.13 oxalomalate lyase
EC 4.1.3.14 L-erythro-3-hydroxyaspartate aldolase
EC 4.1.3.15 now EC 2.2.1.5
EC 4.1.3.16 4-hydroxy-2-oxoglutarate aldolase
EC 4.1.3.17 4-hydroxy-4-methyl-2-oxoglutarate aldolase
EC 4.1.3.18 now EC 2.2.1.6
EC 4.1.3.19 now EC 2.5.1.56
EC 4.1.3.20 now EC 2.5.1.57
EC 4.1.3.21 now EC 2.3.3.14
EC 4.1.3.22 citramalate lyase
EC 4.1.3.23 now EC 2.3.3.2
EC 4.1.3.24 malyl-CoA lyase
EC 4.1.3.25 (S)-citramalyl-CoA lyase
EC 4.1.3.26 3-hydroxy-3-isohexenylglutaryl-CoA lyase
EC 4.1.3.27 anthranilate synthase
EC 4.1.3.28 now EC 2.3.3.3
EC 4.1.3.29 now EC 2.3.3.4
EC 4.1.3.30 methylisocitrate lyase
EC 4.1.3.31 now EC 2.3.3.5
EC 4.1.3.32 2,3-dimethylmalate lyase
EC 4.1.3.33 now EC 2.3.3.6
EC 4.1.3.34 citryl-CoA lyase
EC 4.1.3.35 (1-hydroxycyclohexan-1-yl)acetyl-CoA lyase
EC 4.1.3.36 1,4-dihydroxy-2-naphthoyl-CoA synthase
EC 4.1.3.37 now EC 2.2.1.7
EC 4.1.3.38 aminodeoxychorismate lyase
EC 4.1.3.39 4-hydroxy-2-oxovalerate aldolase
EC 4.1.3.40 chorismate lyase
EC 4.1.3.41 3-hydroxy-D-aspartate aldolase
EC 4.1.3.42 (4S)-4-hydroxy-2-oxoglutarate aldolase
EC 4.1.3.43 4-hydroxy-2-oxohexanoate aldolase
EC 4.1.3.44 tRNA 4-demethylwyosine synthase (AdoMet-dependent)
EC 4.1.3.45 3-hydroxybenzoate synthase
EC 4.1.3.46 (R)-citramalyl-CoA lyase


Entries

EC 4.1.3.1

Accepted name: isocitrate lyase

Reaction: isocitrate = succinate + glyoxylate

For diagram of reaction click here.

Glossary: isocitrate = (1R,2S)-1-hydroxypropane-1,2,3-tricarboxylate (previously known as threo-Ds-isocitrate)

Other name(s): isocitrase; isocitritase; isocitratase; threo-Ds-isocitrate glyoxylate-lyase; isocitrate glyoxylate-lyase

Systematic name: isocitrate glyoxylate-lyase (succinate-forming)

Comments: The isomer of isocitrate involved is (1R,2S)-1-hydroxypropane-1,2,3-tricarboxylate [3].

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9045-78-7

References:

1. McFadden, B.A. and Howes, W.V. Crystallisation and some properties of isocitrate lyase from Pseudomonas indigofera. J. Biol. Chem. 238 (1963) 1737-1742.

2. Shiio, I, Shiio, T. and McFadden, B.A. Isocitrate lyase from Pseudomonas indigofera. I. Preparation, amino acid composition and molecular weight. Biochim. Biophys. Acta 96 (1965) 114-122.

3. Vickery, H.B. A suggested new nomenclature for the isomers of isocitric acid. J. Biol. Chem. 237 (1962) 1739-1741.

[EC 4.1.3.1 created 1961]

[EC 4.1.3.2 Transferred entry: now EC 2.3.3.9, malate synthase (EC 4.1.3.2 created 1961, deleted 2002)]

EC 4.1.3.3

Accepted name: N-acetylneuraminate lyase

Reaction: N-acetylneuraminate = N-acetyl-D-mannosamine + pyruvate

Other name(s): N-acetylneuraminic acid aldolase; acetylneuraminate lyase; sialic aldolase; sialic acid aldolase; sialate lyase; N-acetylneuraminic aldolase; neuraminic aldolase; N-acetylneuraminate aldolase; neuraminic acid aldolase; N-acetylneuraminic acid aldolase; neuraminate aldolase; N-acetylneuraminic lyase; N-acetylneuraminic acid lyase; NPL; NALase; NANA lyase; acetylneuraminate pyruvate-lyase; N-acetylneuraminate pyruvate-lyase

Systematic name: N-acetylneuraminate pyruvate-lyase (N-acetyl-D-mannosamine-forming)

Comments: Also acts on N-glycoloylneuraminate, and on O-acetylated sialic acids, other than 4-O-acetylated derivatives.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9027-60-5

References:

1. Comb, D.G. and Roseman, S. The sialic acids. I. The structure and enzymatic synthesis of N-acetylneuraminic acid. J. Biol. Chem. 235 (1960) 2529-2537.

2. Schauer, R. Chemistry, metabolism, and biological functions of sialic acids. Adv. Carbohydr. Chem. Biochem. 40 (1982) 131-234. [PMID: 6762816]

[EC 4.1.3.3 created 1961]

EC 4.1.3.4

Accepted name: hydroxymethylglutaryl-CoA lyase

Reaction: (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate

For diagram click here.

Other name(s): hydroxymethylglutaryl coenzyme A-cleaving enzyme; hydroxymethylglutaryl coenzyme A lyase; 3-hydroxy-3-methylglutaryl coenzyme A lyase; 3-hydroxy-3-methylglutaryl CoA cleaving enzyme; 3-hydroxy-3-methylglutaryl-CoA lyase; (S)-3-hydroxy-3-methylglutaryl-CoA acetoacetate-lyase

Systematic name: (S)-3-hydroxy-3-methylglutaryl-CoA acetoacetate-lyase (acetyl-CoA-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9030-83-5

References:

1. Bachhawat, B.K., Robinson, W.G. and Coon, M.J. The enzymatic cleavage of β-hydroxy-β-methylglutaryl coenzyme A to acetoacetate and acetyl coenzyme A. J. Biol. Chem. 216 (1955) 727-736.

[EC 4.1.3.4 created 1961]

[EC 4.1.3.5 Transferred entry: now EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase (EC 4.1.3.5 created 1961, deleted 2002)]

EC 4.1.3.6

Accepted name: citrate (pro-3S)-lyase

Reaction: citrate = acetate + oxaloacetate

Other name(s): citrase; citratase; citritase; citridesmolase; citrate aldolase; citric aldolase; citrate lyase; citrate oxaloacetate-lyase, citrate oxaloacetate-lyase [(pro-3S)-CH2COO-→acetate]

Systematic name: citrate oxaloacetate-lyase (forming acetate from the pro-S carboxymethyl group of citrate)

Comments: The enzyme can be dissociated into components, two of which are identical with EC 2.8.3.10 (citrate CoA-transferase) and EC 4.1.3.34 (citryl-CoA lyase). EC 3.1.2.16 (citrate lyase deacetylase), deacetylates and inactivates the enzyme.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9012-83-3

References:

1. Dagley, S. and Dawes, E.A. Citridesmolase: its properties and mode of action. Biochim. Biophys. Acta 17 (1955) 177-184. [PMID: 13239657]

2. Dimroth, P., Loyal, R. and Eggerer, H. Characterization of the isolated transferase subunit of citrate lyase as a CoA-transferase. Evidence ag ainst a covalent enzyme-substrate intermediate. Eur. J. Biochem. 80 (1977) 479-488. [PMID: 336371]

[EC 4.1.3.6 created 1961]

[EC 4.1.3.7 Transferred entry: now EC 2.3.3.1, citrate (Si)-synthase (EC 4.1.3.7 created 1961, deleted 2002)]

[EC 4.1.3.8 Transferred entry: now EC 2.3.3.8, ATP citrate synthase (EC 4.1.3.8 created 1965, modified 1986, deleted 2002)]

[EC 4.1.3.9 Transferred entry: now EC 2.3.3.11, 2-hydroxyglutarate synthase (EC 4.1.3.9 created 1965, deleted 2002)]

[EC 4.1.3.10 Transferred entry: now EC 2.3.3.7, 3-ethylmalate synthase (EC 4.1.3.10 created 1965, modified 1983, deleted 2002)]

[EC 4.1.3.11 Transferred entry: now EC 2.3.3.12, 3-propylmalate synthase (EC 4.1.3.11 created 1972, deleted 2002)]

[EC 4.1.3.12 Transferred entry: now EC 2.3.3.13, 2-isopropylmalate synthase (EC 4.1.3.12 created 1972, deleted 2002)]

EC 4.1.3.13

Accepted name: oxalomalate lyase

Reaction: 3-oxalomalate = oxaloacetate + glyoxylate

Other name(s): 3-oxalomalate glyoxylate-lyase

Systematic name: 3-oxalomalate glyoxylate-lyase (oxaloacetate-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-63-4

References:

1. Sekizawa, Y., Maragoudakis, M.E., King, T.E. and Cheldelin, V.H. Glutamate biosynthesis in an organism lacking a Krebs tricarboxylic acid cycle. V. Isolation of α-hydroxy-γ-ketoglutarate (HKG) in Acetobacter suboxydans. Biochemistry 5 (1966) 2392-2398. [PMID: 6005666]

[EC 4.1.3.13 created 1972]

EC 4.1.3.14

Accepted name: L-erythro-3-hydroxyaspartate aldolase

Reaction: L-erythro-3-hydroxy-aspartate = glycine + glyoxylate

Other name(s): L-erythro-β-hydroxyaspartate aldolase; L-erythro-β-hydroxyaspartate glycine-lyase; erythro-3-hydroxy-Ls-aspartate glyoxylate-lyase

Systematic name: L-erythro-3-hydroxy-aspartate glyoxylate-lyase (glycine-forming)

Comments: A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Paracoccus denitrificans NCIMB 8944, is strictly specific for the L-erythro stereoisomer of 3-hydroxyaspartate. Different from EC 4.1.3.41, erythro-3-hydroxy-D-aspartate aldolase. Requires a divalent cation.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-64-5

References:

1. Gibbs, R.G. and Morris, J.G. Assay and properties of β-hydroxyaspartate aldolase from Micrococcus denitrificans. Biochim. Biophys. Acta 85 (1964) 501-503. [PMID: 14194868]

[EC 4.1.3.14 created 1972, modified 2011]

[EC 4.1.3.15 Transferred entry: now EC 2.2.1.5, 2-hydroxy-3-oxoadipate synthase (EC 4.1.3.15 created 1972, deleted 2002)]

EC 4.1.3.16

Accepted name: 4-hydroxy-2-oxoglutarate aldolase

Reaction: 4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate

Other name(s): 2-oxo-4-hydroxyglutarate aldolase; hydroxyketoglutaric aldolase; 4-hydroxy-2-ketoglutaric aldolase; 2-keto-4-hydroxyglutaric aldolase; 4-hydroxy-2-ketoglutarate aldolase; 2-keto-4-hydroxyglutarate aldolase; 2-oxo-4-hydroxyglutaric aldolase; DL-4-hydroxy-2-ketoglutarate aldolase; hydroxyketoglutarate aldolase; 2-keto-4-hydroxybutyrate aldolase; 4-hydroxy-2-oxoglutarate glyoxylate-lyase; KHGA

Systematic name: 4-hydroxy-2-oxoglutarate glyoxylate-lyase (pyruvate-forming)

Comments: The enzymes from rat liver and bovine liver act on both enantiomers of 4-hydroxy-2-oxoglutarate. cf. EC 4.1.3.42, (4S)-4-hydroxy-2-oxoglutarate aldolase.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9030-81-3

References:

1. Kuratomi, K. and Fukunaga, K. The metabolism of γ-hydroxyglutamate in rat liver. I. Enzymic synthesis of γ-hydroxy-α-ketoglutarate from pyruvate and glyoxalate. Biochim. Biophys. Acta 78 (1963) 617-628.

2. Kobes, R.D. and Dekker, E.E. 2-Keto-4-hydroxyglutarate aldolase of bovine liver. Purification, criteria of purity, and general properties. J. Biol. Chem. 244 (1969) 1919-1925. [PMID: 5780845]

3. Lane, R.S., Shapley, A. and Dekker, E.E. 2-keto-4-hydroxybutyrate aldolase. Identification as 2-keto-4-hydroxyglutarate aldolase, catalytic properties, and role in the mammalian metabolism of L-homoserine. Biochemistry 10 (1971) 1353-1364. [PMID: 5580656]

4. Scholtz, J.M. and Schuster, S.M. Regulation of rat liver 4-hydroxy-2-ketoglutarate aldolase. Biochim. Biophys. Acta 869 (1986) 192-196. [PMID: 3942759]

[EC 4.1.3.16 created 1972 (EC 4.1.2.1 created 1961, incorporated 1972, EC 4.1.2.31 created 1978, incorporated 1982)]

EC 4.1.3.17

Accepted name: 4-hydroxy-4-methyl-2-oxoglutarate aldolase

Reaction: (1) 4-hydroxy-4-methyl-2-oxoglutarate = 2 pyruvate
(2) 2-hydroxy-4-oxobutane-1,2,4-tricarboxylate = oxaloacetate + pyruvate

For diagram of reaction click here.

Other name(s): pyruvate aldolase; γ-methyl-γ-hydroxy-α-ketoglutaric aldolase; 4-hydroxy-4-methyl-2-ketoglutarate aldolase; 4-hydroxy-4-methyl-2-oxoglutarate pyruvate-lyase; HMG aldolase; CHA aldolase; 4-carboxy-4-hydroxy-2-oxoadipate aldolase

Systematic name: 4-hydroxy-4-methyl-2-oxoglutarate pyruvate-lyase (pyruvate-forming)

Comments: Requires a divalent metal ion [3]. This enzyme participates in the degradation of 3,4-dihydroxybenzoate (via the meta-cleavage pathway), phthalate, syringate and 3,4,5-trihydroxybenzoate [1-3]. The enzyme from Pseudomonas straminea can also catalyse the activity of EC 4.1.3.16, 4-hydroxy-2-oxoglutarate aldolase, and the decarboxylation of oxaloacetate [3].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37290-65-6

References:

1. Tack, B.F., Chapman, P.J. and Dagley, S. Purification and properties of 4-hydroxy-4-methyl-2-oxoglutarate aldolase. J. Biol. Chem. 247 (1972) 6444-6449. [PMID: 5076765]

2. Wood, W.A. 2-Keto-3-deoxy-6-phosphogluconic and related aldolases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 7, Academic Press, New York, 1972, pp. 281-302.

3. Maruyama, K. Purification and properties of 4-hydroxy-4-methyl-2-oxoglutarate aldolase from Pseudomonas ochraceae grown on phthalate. J. Biochem. 108 (1990) 327–333. [PMID: 2229032]

4. Nogales, J., Canales, A., Jimenez-Barbero, J., Serra, B., Pingarron, J.M., Garcia, J.L. and Diaz, E. Unravelling the gallic acid degradation pathway in bacteria: the gal cluster from Pseudomonas putida. Mol. Microbiol. 79 (2011) 359-374. [PMID: 21219457]

[EC 4.1.3.17 created 1972, modified 2012]

[EC 4.1.3.18 Transferred entry: now EC 2.2.1.6, acetolactate synthase (EC 4.1.3.18 created 1972, deleted 2002)]

[EC 4.1.3.19 Transferred entry: now EC 2.5.1.56, N-acetylneuraminate synthase (EC 4.1.2.19 created 1972, deleted 2002)]

[EC 4.1.3.20 Transferred entry: now EC 2.5.1.57, N-acylneuraminate-9-phosphate synthase (EC 4.1.3.20 created 1972, deleted 2002)]

[EC 4.1.3.21 Transferred entry: now EC 2.3.3.14, homocitrate synthase (EC 4.1.3.21 created 1972, deleted 2002)]

EC 4.1.3.22

Accepted name: citramalate lyase

Reaction: (2S)-2-hydroxy-2-methylbutanedioate = acetate + pyruvate

For diagram click here.

Glossary: (+)-citramalate = (2S)-2-hydroxy-2-methylbutanedioate

Other name(s): citramalate pyruvate-lyase; citramalate synthase; citramalic-condensing enzyme; citramalate synthetase; citramalic synthase; (S)-citramalate lyase; (+)-citramalate pyruvate-lyase; citramalate pyruvate lyase; (3S)-citramalate pyruvate-lyase; (2S)-2-hydroxy-2-methylbutanedioate pyruvate-lyase

Systematic name: (2S)-2-hydroxy-2-methylbutanedioate pyruvate-lyase (acetate-forming)

Comments: The enzyme can be dissociated into components, two of which are identical with EC 2.8.3.11 (citramalate CoA-transferase) and EC 4.1.3.25 (citramalyl-CoA lyase).

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9027-93-4

References:

1. Barker, H.A. Citramalate lyase of Clostridium tetanomorphum. Arch. Mikrobiol. 59 (1967) 4-12. [PMID: 4301387]

2. Dimroth, P., Buckel, W., Loyal, R. and Eggerer, H. Isolation and function of the subunits of citramalate lyase and formation of hybrids with the subunits of citrate lyase. Eur. J. Biochem. 80 (1977) 469-477. [PMID: 923590]

[EC 4.1.3.22 created 1972]

[EC 4.1.3.23 Transferred entry: now EC 2.3.3.2, decylcitrate synthase (EC 4.1.3.23 created 1972, deleted 2002)]

EC 4.1.3.24

Accepted name: malyl-CoA lyase

Reaction: (1) (S)-malyl-CoA = acetyl-CoA + glyoxylate
(2) (2R,3S)-2-methylmalyl-CoA = propanoyl-CoA + glyoxylate

For diagram of reaction click here.

Glossary: (S)-malyl-CoA = (3S)-3-carboxy-3-hydroxypropanoyl-CoA
(2R,3S)-2-methylmalyl-CoA = L-erythro-β-methylmalyl-CoA = (2R,3S)-2-methyl-3-carboxy-3-hydroxypropanoyl-CoA

Other name(s): malyl-coenzyme A lyase; (3S)-3-carboxy-3-hydroxypropanoyl-CoA glyoxylate-lyase; mclA (gene name); mcl1 (gene name); (3S)-3-carboxy-3-hydroxypropanoyl-CoA glyoxylate-lyase (acetyl-CoA-forming); L-malyl-CoA lyase

Systematic name: (S)-malyl-CoA glyoxylate-lyase (acetyl-CoA-forming)

Comments: The enzymes from Rhodobacter species catalyse a step in the ethylmalonyl-CoA pathway for acetate assimilation [3,5]. The enzyme from halophilic bacteria participate in the methylaspartate cycle and catalyse the reaction in the direction of malyl-CoA formation [6]. The enzyme from the bacterium Chloroflexus aurantiacus, which participates in the 3-hydroxypropanoate cycle for carbon assimilation, also has the activity of EC 4.1.3.25, (3S)-citramalyl-CoA lyase [2,4].

Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, CAS registry number: 37290-67-8

References:

1. Tuboi, S. and Kikuchi, G. Enzymic cleavage of malyl-Coenzyme A into acetyl-Coenzyme A and glyoxylic acid. Biochim. Biophys. Acta 96 (1965) 148-153. [PMID: 14285256]

2. Herter, S., Busch, A. and Fuchs, G. L-Malyl-coenzyme A lyase/β-methylmalyl-coenzyme A lyase from Chloroflexus aurantiacus, a bifunctional enzyme involved in autotrophic CO2 fixation. J. Bacteriol. 184 (2002) 5999-6006. [PMID: 12374834]

3. Meister, M., Saum, S., Alber, B.E. and Fuchs, G. L-malyl-coenzyme A/β-methylmalyl-coenzyme A lyase is involved in acetate assimilation of the isocitrate lyase-negative bacterium Rhodobacter capsulatus. J. Bacteriol. 187 (2005) 1415-1425. [PMID: 15687206]

4. Friedmann, S., Alber, B.E. and Fuchs, G. Properties of R-citramalyl-coenzyme A lyase and its role in the autotrophic 3-hydroxypropionate cycle of Chloroflexus aurantiacus. J. Bacteriol. 189 (2007) 2906-2914. [PMID: 17259315]

5. Erb, T.J., Frerichs-Revermann, L., Fuchs, G. and Alber, B.E. The apparent malate synthase activity of Rhodobacter sphaeroides is due to two paralogous enzymes, (3S)-malyl-coenzyme A (CoA)/β-methylmalyl-CoA lyase and (3S)-malyl-CoA thioesterase. J. Bacteriol. 192 (2010) 1249-1258. [PMID: 20047909]

6. Borjian, F., Han, J., Hou, J., Xiang, H., Zarzycki, J. and Berg, I.A. Malate Synthase and β-Methylmalyl Coenzyme A Lyase Reactions in the Methylaspartate Cycle in Haloarcula hispanica. J. Bacteriol. 199 (2017) . [PMID: 27920298]

[EC 4.1.3.24 created 1972, modified 2014]

EC 4.1.3.25

Accepted name: (S)-citramalyl-CoA lyase

Reaction: (3S)-citramalyl-CoA = acetyl-CoA + pyruvate

For diagram of reaction click here.

Other name(s): citramalyl coenzyme A lyase; (+)-CMA-CoA lyase; (3S)-citramalyl-CoA pyruvate-lyase; Mcl (ambiguous); citramalyl-CoA lyase

Systematic name: (3S)-citramalyl-CoA pyruvate-lyase (acetyl-CoA-forming)

Comments: Requires Mg2+ ions for activity [3]. The enzyme from the bacterium Clostridium tetanomorphum is a component of EC 4.1.3.22, citramalate lyase [2]. It also acts on (3S)-citramalyl thioacyl-carrier protein [2]. The enzyme from the bacterium Chloroflexus aurantiacus also has the activity of EC 4.1.3.24, malyl-CoA lyase [3]. It has no activity with (3R)-citramalyl-CoA (cf. EC 4.1.3.46, (R)-citramalyl-CoA lyase) [3].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37290-68-9

References:

1. Cooper, R.A. and Kornberg, H.L. The utilization of itaconate by Pseudomonas sp. Biochem. J. 91 (1964) 82-91. [PMID: 4284209]

2. Dimroth, P., Buckel, W., Loyal, R. and Eggerer, H. Isolation and function of the subunits of citramalate lyase and formation of hybrids with the subunits of citrate lyase. Eur. J. Biochem. 80 (1977) 469-477. [PMID: 923590]

3. Friedmann, S., Alber, B.E. and Fuchs, G. Properties of R-citramalyl-coenzyme A lyase and its role in the autotrophic 3-hydroxypropionate cycle of Chloroflexus aurantiacus. J. Bacteriol. 189 (2007) 2906-2914. [PMID: 17259315]

[EC 4.1.3.25 created 1972, modified 2014]

EC 4.1.3.26

Accepted name: 3-hydroxy-3-isohexenylglutaryl-CoA lyase

Reaction: 3-hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA = 7-methyl-3-oxooct-6-enoyl-CoA + acetate

Other name(s): β-hydroxy-β-isohexenylglutaryl CoA-lyase; hydroxyisohexenylglutaryl-CoA:acetatelyase; 3-hydroxy-3-isohexenylglutaryl coenzyme A lyase; 3-hydroxy-3-isohexenylglutaryl-CoA isopentenylacetoacetyl-CoA-lyase

Systematic name: 3-hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA acetate-lyase (7-methyl-3-oxooct-6-enoyl-CoA-forming)

Comments: Also acts on the hydroxy derivative of farnesoyl-CoA.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-69-0

References:

1. Seubert, W. and Fass, E. Untersuchungen über den bakterielle Abbau von Isoprenoiden. IV. Reinigung und Eigenschaftender β-Isohexenylglutaconyl-CoA-hydratase und β-Hydroxy-β-isohexenylglutaryl-CoA-lyase. Biochem. Z. 341 (1964) 23-34.

[EC 4.1.3.26 created 1972]

EC 4.1.3.27

Accepted name: anthranilate synthase

Reaction: chorismate + L-glutamine = anthranilate + pyruvate + L-glutamate

For diagram of reaction click here.

Other name(s): anthranilate synthetase; chorismate lyase; chorismate pyruvate-lyase (amino-accepting); TrpE

Systematic name: chorismate pyruvate-lyase (amino-accepting; anthranilate-forming)

Comments: In some organisms, this enzyme is part of a multifunctional protein, together with one or more other components of the system for the biosynthesis of tryptophan [EC 2.4.2.18 (anthranilate phosphoribosyltransferase ), EC 4.1.1.48 (indole-3-glycerol-phosphate synthase), EC 4.2.1.20 (tryptophan synthase) and EC 5.3.1.24 (phosphoribosylanthranilate isomerase)]. The native enzyme in the complex uses either glutamine or, less efficiently, NH3. The enzyme separated from the complex uses NH3 only.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9031-59-8

References:

1. Baker, T. and Crawford, I.P. Anthranilate synthetase. Partial purification and some kinetic studies on the enzyme from Escherichia coli. J. Biol. Chem. 241 (1966) 5577-5584. [PMID: 5333199]

2. Creighton, T.E. and Yanofsky, C. Chorismate to tryptophan (Escherichia coli) - anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase. Methods Enzymol. 17A (1970) 365-380.

3. Hütter, R., Niederberger, P. and DeMoss, J.A. Tryptophan biosynthetic genes in eukaryotic microorganisms. Annu. Rev. Microbiol. 40 (1986) 55-77. [PMID: 16526091]

4. Ito, J. and Yanofsky, C. Anthranilate synthetase, an enzyme specified by the tryptophan operon of Escherichia coli: Comparative studies on the complex and the subunits. J. Bacteriol. 97 (1969) 734-742. [PMID: 4886290]

5. Zalkin, H. and Kling, D. Anthranilate synthetase. Purification and properties of component I from Salmonella typhimurium. Biochemistry 7 (1968) 3566-3573. [PMID: 4878701]

[EC 4.1.3.27 created 1972]

[EC 4.1.3.28 Transferred entry: now EC 2.3.3.3, citrate (Re)-synthase (EC 4.1.3.28 created 1972, deleted 2002)]

[EC 4.1.3.29 Transferred entry: now EC 2.3.3.4, decylhomocitrate synthase (EC 4.1.3.29 created 1976, deleted 2002)]

EC 4.1.3.30

Accepted name: methylisocitrate lyase

Reaction: (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + succinate

Glossary: (2S,3R)-2-methylisocitrate = (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = threo-Ds-2-methylisocitrate

Other name(s): 2-methylisocitrate lyase; MICL; (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase

Systematic name: (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming)

Comments: The enzyme acts on threo-Ds-2-methylisocitrate, but not on threo-Ds-isocitrate, threo-DL-isocitrate or erythro-Ls-isocitrate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 57827-77-7

References:

1. Tabuchi, T. and Satoh, T. Distinction between isocitrate lyase and methylisocitrate lyase in Candida lipolytica. Agric. Biol. Chem. 40 (1976) 1863-1869.

2. Tabuchi, T. and Satoh, T. Purification and properties of methylisocitrate lyase, a key enzyme in propionate metabolism, from Candida lipolytica. Agric. Biol. Chem. 41 (1977) 169-174.

[EC 4.1.3.30 created 1978]

[EC 4.1.3.31 Transferred entry: now EC 2.3.3.5, 2-methylcitrate synthase (EC 4.1.3.31 created 1978, deleted 2002)]

EC 4.1.3.32

Accepted name: 2,3-dimethylmalate lyase

Reaction: (2R,3S)-2,3-dimethylmalate = propanoate + pyruvate

For diagram click here.

Other name(s): 2,3-dimethylmalate pyruvate-lyase

Systematic name: (2R,3S)-2,3-dimethylmalate pyruvate-lyase (propanoate-forming)

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, CAS registry number: 73562-28-4

References:

1. Pirzer, P., Lill, U. and Eggerer, H. Nicotinic acid metabolism. 2,3-Dimethylmalate lyase. Hoppe-Seyler's Z. Physiol. Chem. 360 (1979) 1693-1702. [PMID: 527937]

[EC 4.1.3.32 created 1981]

[EC 4.1.3.33 Transferred entry: now EC 2.3.3.6, 2-ethylmalate synthase (EC 4.1.3.33 created 1983, deleted 2002)]

EC 4.1.3.34

Accepted name: citryl-CoA lyase

Reaction: (3S)-citryl-CoA = acetyl-CoA + oxaloacetate

Other name(s): (3S)-citryl-CoA oxaloacetate-lyase

Systematic name: (3S)-citryl-CoA oxaloacetate-lyase (acetyl-CoA-forming)

Comments: The enzyme is a component of EC 4.1.3.6 {[citrate (pro-3S)-lyase]}and EC 2.3.3.8 [ATP citrate synthase]. Also acts on (3S)-citryl thioacyl-carrier protein.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 131095-35-7

References:

1. Dimroth, P., Loyal, R. and Eggerer, H. Characterization of the isolated transferase subunit of citrate lyase as a CoA-transferase. Evidence against a covalent enzyme-substrate intermediate. Eur. J. Biochem. 80 (1977) 479-488. [PMID: 336371]

2. Lill, U., Schreil, A. and Eggerer, H. Isolation of enzymically active fragments formed by limited proteolysis of ATP citrate lyase. Eur. J. Biochem. 125 (1982) 645-650. [PMID: 6749502]

[EC 4.1.3.34 created 1984, modified 1986]

EC 4.1.3.35

Accepted name: (1-hydroxycyclohexan-1-yl)acetyl-CoA lyase

Reaction: (1-hydroxycyclohexan-1-yl)acetyl-CoA = acetyl-CoA + cyclohexanone

For reaction pathway click here.

Other name(s): (1-hydroxycyclohexan-1-yl)acetyl-CoA cyclohexanone-lyase

Systematic name: (1-hydroxycyclohexan-1-yl)acetyl-CoA cyclohexanone-lyase (acetyl-CoA-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 71343-09-4

References:

1. Ougham, H.J. and Trudgill, P.W. Metabolism of cyclohexaneacetic acid and cyclohexanebutyric acid by Arthrobacter sp. strain CA1. J. Bacteriol. 150 (1982) 1172-1182. [PMID: 7076617]

[EC 4.1.3.35 created 1986]

EC 4.1.3.36

Accepted name: 1,4-dihydroxy-2-naphthoyl-CoA synthase

Reaction: 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA = 1,4-dihydroxy-2-naphthoyl-CoA + H2O

For diagram of reaction, click here.

Other name(s): naphthoate synthase; 1,4-dihydroxy-2-naphthoate synthase; dihydroxynaphthoate synthase; o-succinylbenzoyl-CoA 1,4-dihydroxy-2-naphthoate-lyase (cyclizing); MenB; o-succinylbenzoyl-CoA dehydratase (cyclizing)

Systematic name: 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA dehydratase (cyclizing)

Comments: This enzyme is involved in the synthesis of 1,4-dihydroxy-2-naphthoate, a branch point metabolite leading to the biosynthesis of menaquinone (vitamin K2, in bacteria), phylloquinone (vitamin K1 in plants), and many plant pigments. The coenzyme A group is subsequently removed from the product by EC 3.1.2.28, 1,4-dihydroxy-2-naphthoyl-CoA hydrolase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 61328-42-5

References:

1. Meganathan, R. and Bentley, R. Menaquinone (vitamin K2) biosynthesis: conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid by Mycobacterium phlei enzymes. J. Bacteriol. 140 (1979) 92-98. [PMID: 500558]

2. Kolkmann, R. and Leistner, E. 4-(2'-Carboxyphenyl)-4-oxobutyryl coenzyme A ester, an intermediate in vitamin K2 (menaquinone) biosynthesis. Z. Naturforsch. C: Sci. 42 (1987) 1207-1214. [PMID: 2966501]

3. Johnson, T.W., Shen, G., Zybailov, B., Kolling, D., Reategui, R., Beauparlant, S., Vassiliev, I.R., Bryant, D.A., Jones, A.D., Golbeck, J.H. and Chitnis, P.R. Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. pcc 6803. J. Biol. Chem. 275 (2000) 8523-8530. [PMID: 10722690]

4. Truglio, J.J., Theis, K., Feng, Y., Gajda, R., Machutta, C., Tonge, P.J. and Kisker, C. Crystal structure of Mycobacterium tuberculosis MenB, a key enzyme in vitamin K2 biosynthesis. J. Biol. Chem. 278 (2003) 42352-42360. [PMID: 12909628]

[EC 4.1.3.36 created 1992, modified 2010]

[EC 4.1.3.37 Transferred entry: now EC 2.2.1.7, 1-deoxy-D-xylulose 5-phosphate synthase (EC 4.1.3.37 created 2001, deleted 2002)]

EC 4.1.3.38

Accepted name: aminodeoxychorismate lyase

Reaction: 4-amino-4-deoxychorismate = 4-aminobenzoate + pyruvate

For diagram of reaction click here (folate biosynthesis).

Other name(s): enzyme X; 4-amino-4-deoxychorismate lyase; 4-amino-4-deoxychorismate pyruvate-lyase

Systematic name: 4-amino-4-deoxychorismate pyruvate-lyase (4-aminobenzoate-forming)

Comments: A pyridoxal-phosphate protein. Forms part of the folate biosynthesis pathway. Acts on 4-amino-4-deoxychorismate, the product of EC 6.3.5.8, aminodeoxychorismate synthase, to form p-aminobenzoate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 132264-33-6

References:

1. Ye, Q.Z., Liu, J. and Walsh, C.T. p-Aminobenzoate synthesis in Escherichia coli: purification and characterization of PabB as aminodeoxychorismate synthase and enzyme X as aminodeoxychorismate lyase. Proc. Natl. Acad. Sci. USA 87 (1990) 9391-9395. [PMID: 2251281]

2. Green, J.M., Merkel, W.K. and Nichols, B.P. Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J. Bacteriol. 174 (1992) 5317-5323. [PMID: 1644759]

3. Nakai, T., Mizutani, H., Miyahara, I., Hirotsu, K., Takeda, S., Jhee, K.H., Yoshimura, T. and Esaki, N. Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli. J. Biochem. 128 (2000) 29-38. [PMID: 10876155]

[EC 4.1.3.38 created 2003]

EC 4.1.3.39

Accepted name: 4-hydroxy-2-oxovalerate aldolase

Reaction: (S)-4-hydroxy-2-oxopentanoate = acetaldehyde + pyruvate

For diagram of reaction click here and another click here and another.

Glossary: (S)-4-hydroxy-2-oxopentanoate = (S)-4-hydroxy-2-oxovalerate

Other name(s): 4-hydroxy-2-ketovalerate aldolase; HOA; DmpG; 4-hydroxy-2-oxovalerate pyruvate-lyase; 4-hydroxy-2-oxopentanoate pyruvate-lyase; BphI; 4-hydroxy-2-oxopentanoate pyruvate-lyase (acetaldehyde-forming)

Systematic name: (S)-4-hydroxy-2-oxopentanoate pyruvate-lyase (acetaldehyde-forming)

Comments: Requires Mn2+ for maximal activity [1]. The enzyme from the bacterium Pseudomonas putida is also stimulated by NADH [1]. In some bacterial species the enzyme forms a bifunctional complex with EC 1.2.1.10, acetaldehyde dehydrogenase (acetylating). The enzymes from the bacteria Burkholderia xenovorans and Thermus thermophilus also perform the reaction of EC 4.1.3.43, 4-hydroxy-2-oxohexanoate aldolase [4,5].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 37325-52-3

References:

1. Manjasetty, B.A., Powlowski, J. and Vrielink, A. Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate. Proc. Natl. Acad. Sci. USA 100 (2003) 6992-6997. [PMID: 12764229]

2. Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. J. Bacteriol. 175 (1993) 377-385. [PMID: 8419288]

3. Manjasetty, B.A., Croteau, N., Powlowski, J. and Vrielink, A. Crystallization and preliminary X-ray analysis of dmpFG-encoded 4-hydroxy-2-ketovalerate aldolase—aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. Acta Crystallogr. D Biol. Crystallogr. 57 (2001) 582-585. [PMID: 11264589]

[EC 4.1.3.39 created 2006, modified 2011]

EC 4.1.3.40

Accepted name: chorismate lyase

Reaction: chorismate = 4-hydroxybenzoate + pyruvate

For diagram of reaction click here.

Other name(s): CL; CPL; UbiC

Systematic name: chorismate pyruvate-lyase (4-hydroxybenzoate-forming)

Comments: This enzyme catalyses the first step in the biosynthesis of ubiquinone in Escherichia coli and other Gram-negative bacteria [1]. The yeast Saccharomyces cerevisiae can synthesize ubiquinone from either chorismate or tyrosine [3].

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

References:

1. Nichols, B.P. and Green, J.M. Cloning and sequencing of Escherichia coli ubiC and purification of chorismate lyase. J. Bacteriol. 174 (1992) 5309-5316. [PMID: 1644758]

2. Siebert, M., Severin, K. and Heide, L. Formation of 4-hydroxybenzoate in Escherichia coli: characterization of the ubiC gene and its encoded enzyme chorismate pyruvate-lyase. Microbiology 140 (1994) 897-904. [PMID: 8012607]

3. Meganathan, R. Ubiquinone biosynthesis in microorganisms. FEMS Microbiol. Lett. 203 (2001) 131-139. [PMID: 11583838]

4. Baker, P., Carere, J. and Seah, S.Y.K. Probing the molecular basis of substrate specificity, stereospecificity, and catalysis in the class II pyruvate aldolase, BphI. Biochemistry 50 (2011) 3559-3569. [PMID: 21425833]

5. Baker, P., Hillis, C., Carere, J. and Seah, S.Y.K. Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. Biochemistry 51 (2012) 1942-1952. [PMID: 22316175]

6. Baker, P. and Seah, S.Y.K. Rational design of stereoselectivity in the class II pyruvate aldolase BphI. J. Am. Chem. Soc. 134 (2012) 507-513. [PMID: 22081904]

[EC 4.1.3.40 created 2007]

EC 4.1.3.41

Accepted name: 3-hydroxy-D-aspartate aldolase

Reaction: (1) threo-3-hydroxy-D-aspartate = glycine + glyoxylate
(2) D-erythro-3-hydroxyaspartate = glycine + glyoxylate

Other name(s): D-3-hydroxyaspartate aldolase

Systematic name: 3-hydroxy-D-aspartate glyoxylate-lyase (glycine-forming)

Comments: A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Paracoccus denitrificans IFO 13301, is strictly D-specific as to the α-position of the substrate, but accepts both the threo and erythro forms at the β-position. The erythro form is a far better substrate (about 100 fold). The enzyme can also accept D-allothreonine, D-threonine, erythro-3-phenyl-D-serine and threo-3-phenyl-D-serine. Different from EC 4.1.3.14, erythro-3-hydroxy-L-aspartate aldolase. Requires a divalent cation, such as Mg2+, Mn2+ or Co2+.

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

References:

1. Liu, J.Q., Dairi, T., Itoh, N., Kataoka, M. and Shimizu, S. A novel enzyme, D-3-hydroxyaspartate aldolase from Paracoccus denitrificans IFO 13301: purification, characterization, and gene cloning. Appl. Microbiol. Biotechnol. 62 (2003) 53-60. [PMID: 12835921]

[EC 4.1.3.41 created 2011]

EC 4.1.3.42

Accepted name: (4S)-4-hydroxy-2-oxoglutarate aldolase

Reaction: (4S)-4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate

Glossary: (4S)-4-hydroxy-2-oxoglutatrate = (S)-2-hydroxy-4-oxopentanedioate = L-4-hydroxy-2-oxoglutarate

Other name(s): 2-oxo-4-hydroxyglutarate aldolase (ambiguous); hydroxyketoglutaric aldolase (ambiguous); 4-hydroxy-2-ketoglutaric aldolase (ambiguous); 2-keto-4-hydroxyglutaric aldolase (ambiguous); 4-hydroxy-2-ketoglutarate aldolase (ambiguous); 2-keto-4-hydroxyglutarate aldolase (ambiguous); 2-oxo-4-hydroxyglutaric aldolase (ambiguous); hydroxyketoglutarate aldolase (ambiguous); 2-keto-4-hydroxybutyrate aldolase (ambiguous); 4-hydroxy-2-oxoglutarate glyoxylate-lyase (ambiguous); eda (gene name)

Systematic name: (4S)-4-hydroxy-2-oxoglutarate glyoxylate-lyase (pyruvate-forming)

Comments: The enzyme from the bacterium Escherichia coli is specific for the (S)-enantiomer, is trifunctional, and also catalyses the reaction ofEC 4.1.2.14, 2-dehydro-3-deoxy-phosphogluconate aldolase, and the β-decarboxylation of oxaloacetate. cf. EC 4.1.3.16, 4-hydroxy-2-oxoglutarate aldolase.

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

References:

1. Nishihara, H. and Dekker, E.E. Purification, substrate specificity and binding, β-decarboxylase activity, and other properties of Escherichia coli 2-keto-4-hydroxyglutarate aldolase. J. Biol. Chem. 247 (1972) 5079-5087. [PMID: 4560498]

2. Patil, R.V. and Dekker, E.E. Cloning, nucleotide sequence, overexpression, and inactivation of the Escherichia coli 2-keto-4-hydroxyglutarate aldolase gene. J. Bacteriol. 174 (1992) 102-107. [PMID: 1339418]

[EC 4.1.3.42 created 2013]

EC 4.1.3.43

Accepted name: 4-hydroxy-2-oxohexanoate aldolase

Reaction: (S)-4-hydroxy-2-oxohexanoate = propanal + pyruvate

Other name(s): BphI

Systematic name: (S)-4-hydroxy-2-oxohexanoate pyruvate-lyase (propanal-forming)

Comments: Requires Mn2+ for maximal activity [1,2]. The enzymes from the bacteria Burkholderia xenovorans and Thermus thermophilus also perform the reaction of EC 4.1.3.39, 4-hydroxy-2-oxovalerate aldolase [1,2,6]. The enzyme forms a bifunctional complex with EC 1.2.1.87, propanal dehydrogenase (CoA-propanoylating), with a tight channel connecting the two subunits [3,4,6].

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

References:

1. Baker, P., Pan, D., Carere, J., Rossi, A., Wang, W. and Seah, S.Y.K. Characterization of an aldolase-dehydrogenase complex that exhibits substrate channeling in the polychlorinated biphenyls degradation pathway. Biochemistry 48 (2009) 6551-6558. [PMID: 19476337]

2. Wang, W., Baker, P. and Seah, S.Y.K. Comparison of two metal-dependent pyruvate aldolases related by convergent evolution: substrate specificity, kinetic mechanism, and substrate channeling. Biochemistry 49 (2010) 3774-3782. [PMID: 20364820]

3. Baker, P., Carere, J. and Seah, S.Y.K. Probing the molecular basis of substrate specificity, stereospecificity, and catalysis in the class II pyruvate aldolase, BphI. Biochemistry 50 (2011) 3559-3569. [PMID: 21425833]

4. Carere, J., Baker, P. and Seah, S.Y.K. Investigating the molecular determinants for substrate channeling in BphI-BphJ, an aldolase-dehydrogenase complex from the polychlorinated biphenyls degradation pathway. Biochemistry 50 (2011) 8407-8416. [PMID: 21838275]

5. Baker, P. and Seah, S.Y.K. Rational design of stereoselectivity in the class II pyruvate aldolase BphI. J. Am. Chem. Soc. 134 (2012) 507-513. [PMID: 22081904]

6. Baker, P., Hillis, C., Carere, J. and Seah, S.Y.K. Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. Biochemistry 51 (2012) 1942-1952. [PMID: 22316175]

[EC 4.1.3.43 created 2013]

EC 4.1.3.44

Accepted name: tRNA 4-demethylwyosine synthase (AdoMet-dependent)

Reaction: N1-methylguanine37 in tRNAPhe + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine37 in tRNAPhe + L-methionine + 5'-deoxyadenosine + CO2 + H2O

For diagram of reaction click here.

Glossary: 4-demethylwyosine = imG-14 = 6-methyl-3-(β-D-ribofuranosyl)-3,5-dihydro-9H-imidazo[1,2-a]purin-9-one

Other name(s): TYW1

Systematic name: tRNAPhe N1-methylguanine,pyruvate acetaldehyde-lyase (tRNAPhe 4-demethylwyosine-forming, decarboxylating, dehydrating)

Comments: This enzyme, which is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes, binds two [4Fe-4S] clusters [3,4]. Carbons C2 and C3 from pyruvate are incorporated into 4-demethylwyosine [3]. The enzyme is found in eukaryotes where it is part of the pathway for wybutosine synthesis, and in archaea, where it is involved in the biosynthesis of archaeal wye bases, such as wyosine, isowyosine, and methylwyosine.

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

References:

1. Goto-Ito, S., Ishii, R., Ito, T., Shibata, R., Fusatomi, E., Sekine, S.I., Bessho, Y. and Yokoyama, S. Structure of an archaeal TYW1, the enzyme catalyzing the second step of wye-base biosynthesis. Acta Crystallogr. D Biol. Crystallogr. 63 (2007) 1059-1068. [PMID: 17881823]

2. Suzuki, Y., Noma, A., Suzuki, T., Senda, M., Senda, T., Ishitani, R. and Nureki, O. Crystal structure of the radical SAM enzyme catalyzing tricyclic modified base formation in tRNA. J. Mol. Biol. 372 (2007) 1204-1214. [PMID: 17727881]

3. Young, A.P. and Bandarian, V. Pyruvate is the source of the two carbons that are required for formation of the imidazoline ring of 4-demethylwyosine. Biochemistry 50 (2011) 10573-10575. [PMID: 22026549]

4. Perche-Letuvée, P., Kathirvelu, V., Berggren, G., Clemancey, M., Latour, J.M., Maurel, V., Douki, T., Armengaud, J., Mulliez, E., Fontecave, M., Garcia-Serres, R., Gambarelli, S. and Atta, M. 4-Demethylwyosine synthase from Pyrococcus abyssi is a radical-S-adenosyl-L-methionine enzyme with an additional [4Fe-4S]2+ cluster that interacts with the pyruvate co-substrate. J. Biol. Chem. 287 (2012) 41174-41185. [PMID: 23043105]

[EC 4.1.3.44 created 2013]

EC 4.1.3.45

Accepted name: 3-hydroxybenzoate synthase

Reaction: chorismate = 3-hydroxybenzoate + pyruvate

For diagram of reaction, click here

Glossary: chorismate = (3R,4R)-3-[(1-carboxyethenyl)oxy]-4-hydroxycyclohexa-1,5-diene-1-carboxylate

Other name(s): chorismatase/3-hydroxybenzoate synthase; hyg5 (gene name); bra8 (gene name); XanB2

Systematic name: chorismate pyruvate-lyase (3-hydroxybenzoate-forming)

Comments: The enzyme, found in several bacterial species is involved in biosynthesis of secondary products. The enzyme from the bacterium Xanthomonas campestris pv. campestris also has the activity of EC 4.1.3.40, chorismate lyase [3].

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

References:

1. Andexer, J.N., Kendrew, S.G., Nur-e-Alam, M., Lazos, O., Foster, T.A., Zimmermann, A.S., Warneck, T.D., Suthar, D., Coates, N.J., Koehn, F.E., Skotnicki, J.S., Carter, G.T., Gregory, M.A., Martin, C.J., Moss, S.J., Leadlay, P.F. and Wilkinson, B. Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate. Proc. Natl. Acad. Sci. USA 108 (2011) 4776-4781. [PMID: 21383123]

2. Jiang, Y., Wang, H., Lu, C., Ding, Y., Li, Y. and Shen, Y. Identification and characterization of the cuevaene A biosynthetic gene cluster in Streptomyces sp. LZ35. ChemBioChem. 14 (2013) 1468-1475. [PMID: 23824670]

3. Zhou, L., Wang, J.Y., Wang, J., Poplawsky, A., Lin, S., Zhu, B., Chang, C., Zhou, T., Zhang, L.H. and He, Y.W. The diffusible factor synthase XanB2 is a bifunctional chorismatase that links the shikimate pathway to ubiquinone and xanthomonadins biosynthetic pathways. Mol. Microbiol. 87 (2013) 80-93. [PMID: 23113660]

[EC 4.1.3.45 created 2013]

EC 4.1.3.46

Accepted name: (R)-citramalyl-CoA lyase

Reaction: (3R)-citramalyl-CoA = acetyl-CoA + pyruvate

Other name(s): Ccl

Systematic name: (3R)-citramalyl-CoA pyruvate-lyase (acetyl-CoA-forming)

Comments: Requires Mn2+ ions for activity. The enzyme, purified from the bacterium Chloroflexus aurantiacus, has no activity with (3S)-citramalyl-CoA (cf. EC 4.1.3.25, (S)-citramalyl-CoA lyase).

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

References:

1. Friedmann, S., Alber, B.E. and Fuchs, G. Properties of R-citramalyl-coenzyme A lyase and its role in the autotrophic 3-hydroxypropionate cycle of Chloroflexus aurantiacus. J. Bacteriol. 189 (2007) 2906-2914. [PMID: 17259315]

[EC 4.1.3.46 created 2014]


EC 4.1.99 Other Carbon-Carbon Lyases

Contents

EC 4.1.99.1 tryptophanase
EC 4.1.99.2 tyrosine phenol-lyase
EC 4.1.99.3 deoxyribodipyrimidine photo-lyase
EC 4.1.99.4 now EC 3.5.99.7
EC 4.1.99.5 aldehyde oxygenase (deformylating)
EC 4.1.99.6 now EC 4.2.3.6
EC 4.1.99.7 now EC 4.2.3.9
EC 4.1.99.8 now EC 4.2.3.14
EC 4.1.99.9 now EC 4.2.3.15
EC 4.1.99.10 now EC 4.2.3.16
EC 4.1.99.11 benzylsuccinate synthase
EC 4.1.99.12 3,4-dihydroxy-2-butanone-4-phosphate synthase
EC 4.1.99.13 (6-4)DNA photolyase
EC 4.1.99.14 spore photoproduct lyase
EC 4.1.99.15 deleted covered by EC 4.1.99.14
EC 4.1.99.16 geosmin synthase
EC 4.1.99.17 phosphomethylpyrimidine synthase
EC 4.1.99.18 transferred now EC 4.1.99.22 and EC 4.6.1.17
EC 4.1.99.19 2-iminoacetate synthase
EC 4.1.99.20 3-amino-4-hydroxybenzoate synthase
EC 4.1.99.21 transferred now EC 4.2.3.154
EC 4.1.99.22 GTP 3',8-cyclase
EC 4.1.99.23 5-hydroxybenzimidazole synthase
EC 4.1.99.24 L-tyrosine isonitrile synthase
EC 4.1.99.25 L-tryptophan isonitrile synthase

Entries

EC 4.1.99.1

Accepted name: tryptophanase

Reaction: L-tryptophan + H2O = indole + pyruvate + NH3 (overall reaction)
(1a) L-tryptophan = indole + 2-aminoprop-2-enoate
(1b) 2-aminoprop-2-enoate = 2-iminopropanoate (spontaneous)
(1c) 2-iminopropanoate + H2O = pyruvate + NH3 (spontaneous)

Other name(s): L-tryptophanase; L-tryptophan indole-lyase (deaminating); TNase

Systematic name: L-tryptophan indole-lyase (deaminating; pyruvate-forming)

Comments: A pyridoxal-phosphate protein, requiring K+. The enzyme cleaves a carbon-carbon bond, releasing indole and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form pyruvate and ammonia. The latter reaction, which can occur spontaneously, can also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. Also catalyses 2,3-elimination and β-replacement reactions of some indole-substituted tryptophan analogues of L-cysteine, L-serine and other 3-substituted amino acids.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9024-00-4

References:

1. Burns, R.O. and DeMoss, R.D. Properties of tryptophanase from Escherichia coli. Biochim. Biophys. Acta 65 (1962) 233-244. [PMID: 14017164]

2. Newton, W.A., Morino, Y. and Snell, E.E. Properties of crystalline tryptophanase. J. Biol. Chem. 240 (1965) 1211-1218. [PMID: 14284727]

3. Cowell, J.L., Maser, K. and DeMoss, R.D. Tryptophanase from Aeromonas liquifaciens. Purification, molecular weight and some chemical, catalytic and immunological properties. Biochim. Biophys. Acta 315 (1973) 449-463.

4. Snell, E.E. Tryptophanase: structure, catalytic activities, and mechanism of action. Adv. Enzymol. Relat. Areas Mol. Biol. 42 (1975) 287-333. [PMID: 236639]

[EC 4.1.99.1 created 1972]

EC 4.1.99.2

Accepted name: tyrosine phenol-lyase

Reaction: L-tyrosine + H2O = phenol + pyruvate + NH3 (overall reaction)
(1a) L-tyrosine = phenol + 2-aminoprop-2-enoate
(1b) 2-aminoprop-2-enoate = 2-iminopropanoate (spontaneous)
(1c) 2-iminopropanoate + H2O = pyruvate + NH3 (spontaneous)

Other name(s): β-tyrosinase; L-tyrosine phenol-lyase (deaminating)

Systematic name: L-tyrosine phenol-lyase (deaminating; pyruvate-forming)

Comments: A pyridoxal-phosphate protein. The enzyme cleaves a carbon-carbon bond, releasing phenol and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form pyruvate and ammonia. The latter reaction, which can occur spontaneously, can also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. The enzyme also slowly catalyses similar reactions with D-tyrosine, S-methyl-L-cysteine, L-cysteine, L-serine and D-serine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9059-31-8

References:

1. Kumagai, H., Yamada, H., Matsui, H., Ohkishi, H. and Ogata, K. Tyrosine phenol lyase. I. Purification, crystallization, and properties. J. Biol. Chem. 245 (1970) 1767-1772. [PMID: 4908868]

2. Kumagai, H., Yamada, H., Matsui, H., Ohkishi, H. and Ogata, K. Tyrosine phenol lyase. II. Cofactor requirements. J. Biol. Chem. 245 (1970) 1773-1777. [PMID: 4908869]

[EC 4.1.99.2 created 1972]

EC 4.1.99.3

Accepted name: deoxyribodipyrimidine photo-lyase

Reaction: cyclobutadipyrimidine (in DNA) = 2 pyrimidine residues (in DNA)

For diagram click here.

Other name(s): photoreactivating enzyme; DNA photolyase; DNA-photoreactivating enzyme; DNA cyclobutane dipyrimidine photolyase; DNA photolyase; deoxyribonucleic photolyase; deoxyribodipyrimidine photolyase; photolyase; PRE; PhrB photolyase; deoxyribonucleic cyclobutane dipyrimidine photolyase; phr A photolyase; dipyrimidine photolyase (photosensitive); deoxyribonucleate pyrimidine dimer lyase (photosensitive)

Systematic name: deoxyribocyclobutadipyrimidine pyrimidine-lyase

Comments: A flavoprotein (FAD), containing a second chromophore group. The enzyme catalyses the reactivation by light of irradiated DNA. A similar reactivation of irradiated RNA is probably due to a separate enzyme.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37290-70-3

References:

1. Eker, A.P.M. and Fichtinger-Schepman, A.M.J. Studies on a DNA photoreactivating enzyme from Streptomyces griseus. II. Purification of the enzyme. Biochim. Biophys. Acta 378 (1975) 54-63. [PMID: 804322]

2. Sancar, G.B., Smith, F.W., Reid, R., Payne, G., Levy, M. and Sancar, A. Action mechanism of Escherichia coli DNA photolyase. I. Formation of the enzyme-substrate complex. J. Biol. Chem. 262 (1987) 478-485. [PMID: 3539939]

3. Setlow, J.K. and Bollum, F.J. The minimum size of the substrate for yeast photoreactivating enzyme. Biochim. Biophys. Acta 157 (1968) 233-237. [PMID: 5649902]

[EC 4.1.99.3 created 1972]

[EC 4.1.99.4 Transferred entry: now EC 3.5.99.7, 1-aminocyclopropane-1-carboxylate deaminase (EC 4.1.99.4 created 1981, deleted 2002)]

EC 4.1.99.5

Accepted name: aldehyde oxygenase (deformylating)

Reaction: a long-chain aldehyde + O2 + 2 NADPH + 2 H+ = an alkane + formate + H2O + 2 NADP+

Glossary: a long-chain aldehyde = an aldehyde derived from a fatty acid with an aliphatic chain of 13-22 carbons.

Other name(s): decarbonylase; aldehyde decarbonylase; octadecanal decarbonylase

Systematic name: octadecanal alkane-lyase

Comments: Contains a diiron center. Involved in the biosynthesis of alkanes. The enzyme from the cyanobacterium Nostoc punctiforme PCC 73102 is only active in vitro in the presence of ferredoxin, ferredoxin reductase and NADPH, and produces mostly C15 and C17 alkanes [2,3]. The enzyme from pea (Pisum sativum) produces alkanes of chain length C18 to C32 and is inhibited by metal-chelating agents [1]. The substrate for this enzyme is formed by EC 1.2.1.80, acyl-[acyl-carrier protein] reductase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 94185-90-7

References:

1. Cheesbrough, T.M. and, K olattukudy, P.E. Alkane biosynthesis by decarbonylation of aldehydes catalyzed by a particulate preparation from Pisum sativum. Proc. Natl. Acad. Sci. USA 81 (1984) 6613-6617. [PMID: 6593720]

2. Schirmer, A., Rude, M.A., Li, X., Popova, E. and del Cardayre, S.B. Microbial biosynthesis of alkanes. Science 329 (2010) 559-562. [PMID: 20671186]

3. Warui, D.M., Li, N., Nørgaard, H., Krebs, C., Bollinger, J.M. and Booker, S.J. Detection of formate, rather than carbon monoxide, as the stoichiometric coproduct in conversion of fatty aldehydes to alkanes by a cyanobacterial aldehyde decarbonylase. J. Am. Chem. Soc. 133 (2011) 3316-3319. [PMID: 21341652]

4. Li, N., Chang, W.C., Warui, D.M., Booker, S.J., Krebs, C. and Bollinger, J.M., Jr. Evidence for only oxygenative cleavage of aldehydes to alk(a/e)nes and formate by cyanobacterial aldehyde decarbonylases. Biochemistry 51 (2012) 7908-7916. [PMID: 22947199]

[EC 4.1.99.5 created 1989, modified 2011, modified 2013]

[EC 4.1.99.6 Transferred entry: now EC 4.2.3.6, trichodiene synthase (EC 4.1.99.6 created 1989, deleted 2000)]

[EC 4.1.99.7 Transferred entry: now EC 4.2.3.9, aristolochene synthase (EC 4.1.99.7 created 1992 as EC 2.5.1.40, transferred 1999 to EC 4.1.99.7, deleted 2000)]

[EC 4.1.99.8 Transferred entry: now EC 4.2.3.14, pinene synthase (EC 4.1.99.8 created 2000, deleted 2000)]

[EC 4.1.99.9 Transferred entry: now EC 4.2.3.15, myrcene synthase (EC 4.1.99.9 created 2000, deleted 2000)]

[EC 4.1.99.10 Transferred entry: now EC 4.2.3.16, trichodiene synthase (EC 4.1.99.10 created 2000, deleted 2000)]

EC 4.1.99.11

Accepted name: benzylsuccinate synthase

Reaction: benzylsuccinate = toluene + fumarate

For diagram of reaction click here.

Other name(s): benzylsuccinate fumarate-lyase

Systematic name: benzylsuccinate fumarate-lyase (toluene-forming)

Comments: A glycyl radical enzyme that is inhibited by benzyl alcohol, benzaldehyde, phenylhydrazine and is inactivated by oxygen.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, UM-BBD, CAS registry number: 209264-18-6

References:

1. Beller, H.R. and Spormann, A.M. Analysis of the novel benzylsuccinate synthase reaction for anaerobic toluene activation based on structural studies of the product. J. Bacteriol. 180 (1998) 5454-5457. [PMID: 9765580]

2. Leuthner, B., Leutwein, C., Schultz, H., Hörth, P., Haehnel, W., Schiltz, E., Schägger, H. and Heider, J. Biochemical and genetic characterisation of benzylsuccinate synthase from Thauera aromatica: a new glycyl radical enzyme catalysing the first step in anaerobic toluene metabolism. Mol. Microbiol. 28 (1998) 615-628. [PMID: 9632263]

[EC 4.1.99.11 created 2000]

EC 4.1.99.12

Accepted name: 3,4-dihydroxy-2-butanone-4-phosphate synthase

Reaction: D-ribulose 5-phosphate = formate + L-3,4-dihydroxybutan-2-one 4-phosphate

For diagram of reaction click here

Other name(s): DHBP synthase; L-3,4-dihydroxybutan-2-one-4-phosphate synthase

Systematic name: D-ribulose 5-phosphate formate-lyase (L-3,4-dihydroxybutan-2-one 4-phosphate-forming)

Comments: Requires a divalent cation, preferably Mg2+, for activity [1]. The reaction involves an intramolecular skeletal rearrangement, with the bonds in D-ribulose 5-phosphate that connect C-3 and C-5 to C-4 being broken, C-4 being removed as formate and reconnection of C-3 and C-5 [1]. The phosphorylated four-carbon product (L-3,4-dihydroxybutan-2-one 4-phosphate) is an intermediate in the biosynthesis of riboflavin [1].

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

References:

1. Volk, R. and Bacher, A. Studies on the 4-carbon precursor in the biosynthesis of riboflavin. Purification and properties of L-3,4-dihydroxy-2-butanone-4-phosphate synthase. J. Biol. Chem. 265 (1990) 19479-19485. [PMID: 2246238]

2. Liao, D.I., Calabrese, J.C., Wawrzak, Z., Viitanen, P.V. and Jordan, D.B. Crystal structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase of riboflavin biosynthesis. Structure 9 (2001) 11-18. [PMID: 11342130]

3. Kelly, M.J., Ball, L.J., Krieger, C., Yu, Y., Fischer, M., Schiffmann, S., Schmieder, P., Kühne, R., Bermel, W., Bacher, A., Richter, G. and Oschkinat, H. The NMR structure of the 47-kDa dimeric enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase and ligand binding studies reveal the location of the active site. Proc. Natl. Acad. Sci. USA 98 (2001) 13025-13030. [PMID: 11687623]

4. Liao, D.I., Zheng, Y.J., Viitanen, P.V. and Jordan, D.B. Structural definition of the active site and catalytic mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase. Biochemistry 41 (2002) 1795-1806. [PMID: 11827524]

5. Fischer, M., Römisch, W., Schiffmann, S., Kelly, M., Oschkinat, H., Steinbacher, S., Huber, R., Eisenreich, W., Richter, G. and Bacher, A. Biosynthesis of riboflavin in archaea studies on the mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase of Methanococcus jannaschii. J. Biol. Chem. 277 (2002) 41410-41416. [PMID: 12200440]

6. Steinbacher, S., Schiffmann, S., Richter, G., Huber, R., Bacher, A. and Fischer, M. Structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase from Methanococcus jannaschii in complex with divalent metal ions and the substrate ribulose 5-phosphate: implications for the catalytic mechanism. J. Biol. Chem. 278 (2003) 42256-42265. [PMID: 12904291]

7. Steinbacher, S., Schiffmann, S., Bacher, A. and Fischer, M. Metal sites in 3,4-dihydroxy-2-butanone 4-phosphate synthase from Methanococcus jannaschii in complex with the substrate ribulose 5-phosphate. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 1338-1340. [PMID: 15213409]

8. Echt, S., Bauer, S., Steinbacher, S., Huber, R., Bacher, A. and Fischer, M. Potential anti-infective targets in pathogenic yeasts: structure and properties of 3,4-dihydroxy-2-butanone 4-phosphate synthase of Candida albicans. J. Mol. Biol. 341 (2004) 1085-1096. [PMID: 15328619]

[EC 4.1.99.12 created 2007]

EC 4.1.99.13

Accepted name: (6-4)DNA photolyase

Reaction: (6-4) photoproduct (in DNA) = 2 pyrimidine residues (in DNA)

For diagram of reaction, click here.

Other name(s): DNA photolyase; H64PRH; NF-10; phr (6-4); PL-(6-4); OtCPF1; (6-4) PHR; At64PHR

Systematic name: (6-4) photoproduct pyrimidine-lyase

Comments: A flavoprotein (FAD). The overall repair reaction consists of two distinct steps, one of which is light-independent and the other one light-dependent. In the initial light-independent step, a 6-iminium ion is thought to be generated via proton transfer induced by two histidines highly conserved among the (6-4) photolyases. This intermediate spontaneously rearranges to form an oxetane intermediate by intramolecular nucleophilic attack. In the subsequent light-driven reaction, one electron is believed to be transferred from the fully reduced FAD cofactor (FADH-) to the oxetane intermediate thus forming a neutral FADH radical and an anionic oxetane radical, which spontaneously fractures. The excess electron is then back-transferred to the flavin radical restoring the fully reduced flavin cofactor and a pair of pyrimidine bases [2].

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

References:

1. Hitomi, K., DiTacchio, L., Arvai, A.S., Yamamoto, J., Kim, S.T., Todo, T., Tainer, J.A., Iwai, S., Panda, S. and Getzoff, E.D. Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes. Proc. Natl. Acad. Sci. USA 106 (2009) 6962-6967. [PMID: 19359474]

2. Schleicher, E., Hitomi, K., Kay, C.W., Getzoff, E.D., Todo, T. and Weber, S. Electron nuclear double resonance differentiates complementary roles for active site histidines in (6-4) photolyase. J. Biol. Chem. 282 (2007) 4738-4747. [PMID: 17164245]

[EC 4.1.99.13 created 2009]

EC 4.1.99.14

Accepted name: spore photoproduct lyase

Reaction: (5R)-5,6-dihydro-5-(thymidin-7-yl)thymidine (in double-helical DNA) = thymidylyl-(3'→5')-thymidylate (in double-helical DNA)

For diagram of reaction click here

Other name(s): SAM; SP lyase; SPL; SplB; SplG

Systematic name: spore photoproduct pyrimidine-lyase

Comments: This enzyme is a member of the 'AdoMet radical' (radical SAM) family. The enzyme binds a [4Fe-4S] cluster. The cluster is coordinated by 3 cysteines and an exchangeable SAM molecule [3]. The 5'-deoxy-adenosine radical formed after electron transfer from the [4Fe-4S] cluster to the S-adenosyl-L-methionine, initiates the repair by abstracting the C-6 hydrogen of the spore photoproduct lesion. During the second part of the repair process the SAM molecule is regenerated [3].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-70-3

References:

1. Chandor, A., Berteau, O., Douki, T., Gasparutto, D., Sanakis, Y., Ollagnier-de-Choudens, S., Atta, M. and Fontecave, M. Dinucleotide spore photoproduct, a minimal substrate of the DNA repair spore photoproduct lyase enzyme from Bacillus subtilis. J. Biol. Chem. 281 (2006) 26922-26931. [PMID: 16829676]

2. Pieck, J.C., Hennecke, U., Pierik, A.J., Friedel, M.G. and Carell, T. Characterization of a new thermophilic spore photoproduct lyase from Geobacillus stearothermophilus (SplG) with defined lesion containing DNA substrates. J. Biol. Chem. 281 (2006) 36317-36326. [PMID: 16968710]

3. Buis, J.M., Cheek, J., Kalliri, E. and Broderick, J.B. Characterization of an active spore photoproduct lyase, a DNA repair enzyme in the radical S-adenosylmethionine superfamily. J. Biol. Chem. 281 (2006) 25994-26003. [PMID: 16829680]

4. Mantel, C., Chandor, A., Gasparutto, D., Douki, T., Atta, M., Fontecave, M., Bayle, P.-A., Mouesca, J.-M. and Bardet, M. Combined NMR and DFT studies for the absolute configuration elucidation of the spore photoproduct, a UV-induced DNA lesion. J. Am. Chem. Soc. 130 (2008) 16978-16984. [PMID: 19012397]

5. Silver, S.C., Chandra, T., Zilinskas, E., Ghose, S., Broderick, W.E. and Broderick, J.B. Complete stereospecific repair of a synthetic dinucleotide spore photoproduct by spore photoproduct lyase. J. Biol. Inorg. Chem. 15 (2010) 943-955. [PMID: 20405152]

[EC 4.1.99.14 created 2009, modified 2010]

[EC 4.1.99.15 Deleted entry: S-specific spore photoproduct lyase. This enzyme was classified on the basis of an incorrect reaction. The activity is covered by EC 4.1.99.14, spore photoproduct lyase (EC 4.1.99.15 created 2009, deleted 2010)]

EC 4.1.99.16

Accepted name: geosmin synthase

Reaction: (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O = (–)-geosmin + acetone

For diagram of reaction click here and mechanism click here.

Systematic name: germacradienol geosmin-lyase (acetone forming)

Comments: Requires Mg2+. Geosmin is the cause of the characteristic smell of moist soil. It is a bifunctional enzyme. The N-terminal part of the enzyme is EC 4.2.3.22, germacradienol synthase, and forms germacradienol from farnesyl diphosphate. The C-terminal part of the enzyme catalyses the conversion of germacradienol to geosmin via (1S,4aS,8aS)-1,4a-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene.

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

References:

1. Jiang, J., He, X. and Cane, D.E. Geosmin biosynthesis. Streptomyces coelicolor germacradienol/germacrene D synthase converts farnesyl diphosphate to geosmin. J. Am. Chem. Soc. 128 (2006) 8128-8129. [PMID: 16787064]

2. Cane, D.E., He, X., Kobayashi, S., Omura, S. and Ikeda, H. Geosmin biosynthesis in Streptomyces avermitilis. Molecular cloning, expression, and mechanistic study of the germacradienol/geosmin synthase. J. Antibiot. (Tokyo) 59 (2006) 471-479. [PMID: 17080683]

3. Jiang, J., He, X. and Cane, D.E. Biosynthesis of the earthy odorant geosmin by a bifunctional Streptomyces coelicolor enzyme. Nat. Chem. Biol. 3 (2007) 711-715. [PMID: 17873868]

[EC 4.1.99.16 created 2011]

EC 4.1.99.17

Accepted name: phosphomethylpyrimidine synthase

Reaction: 5-amino-1-(5-phospho-D-ribosyl)imidazole + S-adenosyl-L-methionine = 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + 5'-deoxyadenosine + L-methionine + formate + CO

For diagram of reaction click here.

Other name(s): thiC (gene name)

Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine-forming)

Comments: Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce L-methionine and a 5'-deoxyadenosin-5'-yl radical that is crucial for the conversion of the substrate. Part of the pathway for thiamine biosynthesis.

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

References:

1. Chatterjee, A., Li, Y., Zhang, Y., Grove, T.L., Lee, M., Krebs, C., Booker, S.J., Begley, T.P. and Ealick, S.E. Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat. Chem. Biol. 4 (2008) 758-765. [PMID: 18953358]

2. Martinez-Gomez, N.C., Poyner, R.R., Mansoorabadi, S.O., Reed, G.H. and Downs, D.M. Reaction of AdoMet with ThiC generates a backbone free radical. Biochemistry 48 (2009) 217-219. [PMID: 19113839]

3. Chatterjee, A., Hazra, A.B., Abdelwahed, S., Hilmey, D.G. and Begley, T.P. A "radical dance" in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase. Angew. Chem. Int. Ed. Engl. 49 (2010) 8653-8656. [PMID: 20886485]

[EC 4.1.99.17 created 2011]

[EC 4.1.99.18 Transferred entry: cyclic pyranopterin phosphate synthase. Now known to be catalysed by the combined effort of EC 4.1.99.22, GTP 3,8-cyclase, and EC 4.6.1.17, cyclic pyranopterin monophosphate synthase (EC 4.1.99.18 created 2011, deleted 2016)]

EC 4.1.99.19

Accepted name: 2-iminoacetate synthase

Reaction: L-tyrosine + S-adenosyl-L-methionine + NADPH = 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP+ + H+

For diagram of reaction click here.

Glossary: 4-methylphenol = 4-cresol = p-cresol

Other name(s): thiH (gene name)

Systematic name: L-tyrosine 4-methylphenol-lyase (2-iminoacetate-forming)

Comments: Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce methionine and a 5-deoxyadenosin-5-yl radical that is crucial for the conversion of the substrate. The reductant is assumed to be NADPH, which is provided by a flavoprotein:NADPH oxidoreductase system [4]. Part of the pathway for thiamine biosynthesis.

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

References:

1. Leonardi, R., Fairhurst, S.A., Kriek, M., Lowe, D.J. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: isolation and initial characterisation of the ThiGH complex. FEBS Lett. 539 (2003) 95-99. [PMID: 12650933]

2. Kriek, M., Martins, F., Challand, M.R., Croft, A. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: identification of the intermediate and by-product derived from tyrosine. Angew. Chem. Int. Ed. Engl. 46 (2007) 9223-9226. [PMID: 17969213]

3. Kriek, M., Martins, F., Leonardi, R., Fairhurst, S.A., Lowe, D.J. and Roach, P.L. Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro. J. Biol. Chem. 282 (2007) 17413-17423. [PMID: 17403671]

4. Challand, M.R., Martins, F.T. and Roach, P.L. Catalytic activity of the anaerobic tyrosine lyase required for thiamine biosynthesis in Escherichia coli. J. Biol. Chem. 285 (2010) 5240-5248. [PMID: 19923213]

[EC 4.1.99.19 created 2011, modified 2014]

EC 4.1.99.20

Accepted name: 3-amino-4-hydroxybenzoate synthase

Reaction: 2-amino-4,5-dihydroxy-6-oxo-7-(phosphooxy)heptanoate = 3-amino-4-hydroxybenzoate + phosphate + 2 H2O

For diagram of reaction click here.

Other name(s): 3,4-AHBA synthase; griH (gene name)

Systematic name: 2-amino-4,5-dihydroxy-6-oxo-7-(phosphooxy)heptanoate hydro-lyase (cyclizing, 3-amino-4-hydroxybenzoate-forming)

Comments: Requires Mn2+ for maximum activity. The reaction is suggested to take place in several steps. Schiff base formation, double bond migration and dephosphorylation followed by ring opening and closing to form a pyrrolidine ring, and finally dehydration to form the product 3-amino-4-hydroxybenzoate. In the bacterium Streptomyces griseus the enzyme is involved in biosynthesis of grixazone, a yellow pigment that contains a phenoxazinone chromophore.

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

References:

1. Suzuki, H., Ohnishi, Y., Furusho, Y., Sakuda, S. and Horinouchi, S. Novel benzene ring biosynthesis from C3 and C4 primary metabolites by two enzymes. J. Biol. Chem. 281 (2006) 36944-36951. [PMID: 17003031]

[EC 4.1.99.20 created 2013, modified 2016]

[EC 4.1.99.21 Transferred entry: (5-formylfuran-3-yl)methyl phosphate synthase. Now EC 4.2.3.153 (5-formylfuran-3-yl)methyl phosphate synthase. (EC 4.1.99.21 created 2015, deleted 2015)]

EC 4.1.99.22

Accepted name: GTP 3',8-cyclase

Reaction: GTP + S-adenosyl-L-methionine + reduced electron acceptor = (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + L-methionine + oxidized electron acceptor

For diagram of reaction click here.

Other name(s): MOCS1A (gene name); moaA (gene name); cnx2 (gene name)

Systematic name: GTP 3',8-cyclase [(8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate-forming]

Comments: The enzyme catalyses an early step in the biosynthesis of the molybdenum cofactor (MoCo). In bacteria and plants the reaction is catalysed by MoaA and Cnx2, respectively. In mammals it is catalysed by the MOCS1A domain of the bifunctional MOCS1 protein, which also catalyses EC 4.6.1.17, cyclic pyranopterin monophosphate synthase. The enzyme belongs to the superfamily of radical S-adenosyl-L-methionine (radical SAM) enzymes, and contains two oxygen-sensitive FeS clusters.

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

References:

1. Hänzelmann, P., Hernandez, H.L., Menzel, C., Garcia-Serres, R., Huynh, B.H., Johnson, M.K., Mendel, R.R. and Schindelin, H. Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. J. Biol. Chem. 279 (2004) 34721-34732. [PMID: 15180982]

2. Hänzelmann, P. and Schindelin, H. Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans. Proc. Natl. Acad. Sci. USA 101 (2004) 12870-12875. [PMID: 15317939]

3. Hänzelmann, P. and Schindelin, H. Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism. Proc. Natl. Acad. Sci. USA 103 (2006) 6829-6834. [PMID: 16632608]

4. Lees, N.S., Hänzelmann, P., Hernandez, H.L., Subramanian, S., Schindelin, H., Johnson, M.K. and Hoffman, B.M. ENDOR spectroscopy shows that guanine N1 binds to [4Fe-4S] cluster II of the S-adenosylmethionine-dependent enzyme MoaA: mechanistic implications. J. Am. Chem. Soc. 131 (2009) 9184-9185. [PMID: 19566093]

5. Hover, B.M., Loksztejn, A., Ribeiro, A.A. and Yokoyama, K. Identification of a cyclic nucleotide as a cryptic intermediate in molybdenum cofactor biosynthesis. J. Am. Chem. Soc. 135 (2013) 7019-7032. [PMID: 23627491]

6. Hover, B.M. and Yokoyama, K. C-Terminal glycine-gated radical initiation by GTP 3',8-cyclase in the molybdenum cofactor biosynthesis. J. Am. Chem. Soc. 137 (2015) 3352-3359. [PMID: 25697423]

7. Hover, B.M., Tonthat, N.K., Schumacher, M.A. and Yokoyama, K. Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis. Proc. Natl. Acad. Sci. USA 112 (2015) 6347-6352. [PMID: 25941396]

[EC 4.1.99.22 created 2011 as EC 4.1.99.18, part transferred 2016 to EC 4.1.99.22]

EC 4.1.99.23

Accepted name: 5-hydroxybenzimidazole synthase

Reaction: 5-amino-1-(5-phospho-β-D-ribosyl)imidazole + S-adenosyl-L-methionine + reduced acceptor = 5-hydroxybenzimidazole + 5'-deoxyadenosine + L-methionine + formate + NH3 + phosphate + oxidized acceptor

For diagram of reaction click here

Other name(s): bzaF (gene name); HBI synthase

Systematic name: 5-amino-1-(5-phospho-β-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine-forming)

Comments: The enzyme, purified from bacteria, is part of the anaerobic pathway for cobalamin biosynthesis. It binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce L-methionine and a 5'-deoxyadenosin-5'-yl radical that is crucial for the conversion of the substrate.

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

References:

1. Mehta, A.P., Abdelwahed, S.H., Fenwick, M.K., Hazra, A.B., Taga, M.E., Zhang, Y., Ealick, S.E. and Begley, T.P. Anaerobic 5-hydroxybenzimidazole formation from aminoimidazole ribotide: an unanticipated intersection of thiamin and vitamin B12 biosynthesis. J. Am. Chem. Soc. 137 (2015) 10444-10447. [PMID: 26237670]

2. Hazra, A.B., Han, A.W., Mehta, A.P., Mok, K.C., Osadchiy, V., Begley, T.P. and Taga, M.E. Anaerobic biosynthesis of the lower ligand of vitamin B12. Proc. Natl Acad. Sci. USA 112 (2015) 10792-10797. [PMID: 26246619]

[EC 4.1.99.23 created 2017]

EC 4.1.99.24

Accepted name: L-tyrosine isonitrile synthase

Reaction: L-tyrosine + D-ribulose 5-phosphate = (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H2O

For diagram of reaction click here

Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate = L-tyrosine isonitrile
paerucumarin = 6,7-dihydroxy-3-isocyanochromen-2-one
rhabduscin = N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-{4-[(E)-2-isocyanoethenyl]phenoxy}-2-methyloxan-3-yl]acetamide

Other name(s): pvcA (gene name)

Systematic name: L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming)

Comments: The enzymes from the bacteria Pseudomonas aeruginosa and Xenorhabdus nematophila are involved in the biosynthesis of paerucumarin and rhabduscin, respectively. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tyrosine and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.25, L-tryptophan isonitrile synthase.

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

References:

1. Clarke-Pearson, M.F. and Brady, S.F. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J. Bacteriol. 190 (2008) 6927-6930. [PMID: 18689486]

2. Drake, E.J. and Gulick, A.M. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J. Mol. Biol. 384 (2008) 193-205. [PMID: 18824174]

3. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]

[EC 4.1.99.24 created 2018]

EC 4.1.99.25

Accepted name: L-tryptophan isonitrile synthase

Reaction: L-tryptophan + D-ribulose 5-phosphate = (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H2O

For diagram of reaction click here (mechanism)

Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile
hydroxyacetone = 1-hydroxypropan-2-one

Other name(s): isnA (gene name); ambI1 (gene name); well1 (gene name)

Systematic name: L-tryptophan:D-ribulose-5-phosphate lyase (isonitrile-forming)

Comments: The enzymes from cyanobacteria that belong to the Nostocales order participate in the biosynthesis of hapalindole-type alkaloids. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tryptophan and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.24, L-tyrosine isonitrile synthase

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

References:

1. Brady, S.F. and Clardy, J. Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem Int Ed Engl 44 (2005) 7063-7065. [PMID: 16206308]

2. Brady, S.F. and Clardy, J. Systematic investigation of the Escherichia coli metabolome for the biosynthetic origin of an isocyanide carbon atom. Angew Chem Int Ed Engl 44 (2005) 7045-7048. [PMID: 16217820]

3. Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372-377. [PMID: 24180436]

4. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]

[EC 4.1.99.25 created 2018]


Continued with EC 4.2.1.1 to EC 4.2.1.50
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