Enzyme Nomenclature

Continued from EC 1.14.14.101 to EC 1.14.14.170

EC 1.14.15 to EC 1.14.18

EC 1.14 Acting on paired donors with incorporation of molecular oxygen [continued]

EC 1.14.15 With a reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen
EC 1.14.17 With ascorbate as one donor, and incorporation of one atom of oxygen
EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen


EC 1.14.15 With a reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.15.1 camphor 5-monooxygenase
EC 1.14.15.2 now EC 1.14.13.162
EC 1.14.15.3 alkane 1-monooxygenase
EC 1.14.15.4 steroid 11β-monooxygenase
EC 1.14.15.5 corticosterone 18-monooxygenase
EC 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving)
EC 1.14.15.7 choline monooxygenase
EC 1.14.15.8 steroid 15β-monooxygenase
EC 1.14.15.9 spheroidene monooxygenase
EC 1.14.15.10 (+)-camphor 6-endo-hydroxylase
EC 1.14.15.11 pentalenic acid synthase
EC 1.14.15.12 transferred, now EC 1.14.14.46
EC 1.14.15.13 pulcherriminic acid synthase
EC 1.14.15.14 methyl-branched lipid ω-hydroxylase
EC 1.14.15.15 cholestanetriol 26-monooxygenase
EC 1.14.15.16 vitamin D3 24-hydroxylase
EC 1.14.15.17 pheophorbide-a oxygenase
EC 1.14.15.18 calcidiol 1-monooxygenase
EC 1.14.15.19 C-19 steroid 1α-hydroxylase
EC 1.14.15.20 heme oxygenase (biliverdin-producing, ferredoxin)
EC 1.14.15.21 zeaxanthin epoxidase
EC 1.14.15.22 vitamin D 1,25-hydroxylase
EC 1.14.15.23 chloroacetanilide N-alkylformylase
EC 1.14.15.25 p-cymene methyl-monooxygenase
EC 1.14.15.26 toluene methyl-monooxygenase
EC 1.14.15.27 β-dihydromenaquinone-9 ω-hydroxylase
EC 1.14.15.28 cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]
EC 1.14.15.29 cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]
EC 1.14.15.30 3-ketosteroid 9α-monooxygenase

EC 1.14.15.1

Accepted name: camphor 5-monooxygenase

Reaction: (+)-camphor + reduced putidaredoxin + O2 = (+)-exo-5-hydroxycamphor + oxidized putidaredoxin + H2O

For diagram of reaction click here.

Other name(s): camphor 5-exo-methylene hydroxylase; 2-bornanone 5-exo-hydroxylase; bornanone 5-exo-hydroxylase; camphor 5-exo-hydroxylase; camphor 5-exohydroxylase; camphor hydroxylase; d-camphor monooxygenase; methylene hydroxylase; methylene monooxygenase; D-camphor-exo-hydroxylase; camphor methylene hydroxylase

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (5-hydroxylating)

Comments: A heme-thiolate protein (P-450). Also acts on (–)-camphor and 1,2-campholide, forming 5-exo-hydroxy-1,2-campholide.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 9030-82-4

References:

1. Hedegaard, J. and Gunsalus, I.C. Mixed function oxidation. IV. An induced methylene hydroxylase in camphor oxidation. J. Biol. Chem. 240 (1965) 4038-4043. [PMID: 4378858]

2. Tyson, C.A., Lipscomb, J.D. and Gunsalus, I.C. The role of putidaredoxin and P450cam in methylene hydroxylation. J. Biol. Chem. 247 (1972) 5777-5784. [PMID: 4341491]

[EC 1.14.15.1 created 1972, modified 1986]

[EC 1.14.15.2 Transferred entry: camphor 1,2-monooxygenase. Now EC 1.14.13.162, 2,5-diketocamphane 1,2-monooxygenase. (EC 1.14.15.2 created 1972, deleted 2012)]

EC 1.14.15.3

Accepted name: alkane 1-monooxygenase

Reaction: octane + 2 reduced rubredoxin + O2 + 2 H+ = 1-octanol + 2 oxidized rubredoxin + H2O

Other name(s): alkane 1-hydroxylase; ω-hydroxylase; fatty acid ω-hydroxylase; alkane monooxygenase; 1-hydroxylase; alkane hydroxylase

Systematic name: alkane,reduced-rubredoxin:oxygen 1-oxidoreductase

Comments: Some enzymes in this group are heme-thiolate proteins (P-450). Also hydroxylates fatty acids in the ω-position.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 9059-16-9

References:

1. Cardini, G. and Jurtshuk, P. The enzymatic hydroxylation of n-octane by Corynebacterium sp. strain 7E1C. J. Biol. Chem. 245 (1970) 2789-2796. [PMID: 4317878]

2. McKenna, E.J. and Coon, M.J. Enzymatic ω-oxidation. IV. Purification and properties of the ω-hydroxylase of Pseudomonas oleovorans. J. Biol. Chem. 245 (1970) 3882-3889. [PMID: 4395379]

3. Peterson, J.A., Kusunose, M., Kusunose, E. and Coon, M.J. Enzymatic ω-oxidation. II. Function of rubredoxin as the electron carrier in ω-hydroxylation. J. Biol. Chem. 242 (1967) 4334-4340. [PMID: 4294330]

[EC 1.14.15.3 created 1972]

EC 1.14.15.4

Accepted name: steroid 11β-monooxygenase

Reaction: a steroid + 2 reduced adrenodoxin + O2 + 2 H+ = an 11β-hydroxysteroid + 2 oxidized adrenodoxin + H2O

Other name(s): steroid 11β-hydroxylase; steroid 11β/18-hydroxylase

Systematic name: steroid,reduced-adrenodoxin:oxygen oxidoreductase (11β-hydroxylating)

Comments: A heme-thiolate protein (P-450). Also hydroxylates steroids at the 18-position, and converts 18-hydroxycorticosterone into aldosterone.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9029-66-7

References:

1. Grant, J.K. and Brownie, A.C. The role of fumarate and TPN in steroid enzymic 11β-hydroxylation. Biochim. Biophys. Acta 18 (1955) 433-434. [PMID: 13276417]

2. Hayano, M. and Dorfman, R.I. On the mechanism of the C-11β-hydroxylation of steroids. J. Biol. Chem. 211 (1954) 227-235. [PMID: 13211659]

3. Tomkins, G.M., Michael, P.J. and Curran, J.F. Studies on the nature of steroid 11β-hydroxylation. Biochim. Biophys. Acta 23 (1957) 655-656. [PMID: 13426185]

4. Yanagibashi, K., Haniu, M., Shively, J.E., Shen, W.H. and Hall, P. The synthesis of aldosterone by the adrenal cortex. Two zones (fasciculata and glomerulosa) possess one enzyme for 11β-, 18-hydroxylation, and aldehyde synthesis. J. Biol. Chem. 261 (1986) 3556-3562. [PMID: 3485096]

5. Zuidweg, M.H.J. Hydroxylation of Reichstein's compound S with cell-free preparations from Curvularia lunata. Biochim. Biophys. Acta 152 (1968) 144-158. [PMID: 4967077]

[EC 1.14.15.4 created 1961 as EC 1.99.1.7, transferred 1965 to EC 1.14.1.6, transferred 1972 to EC 1.14.15.4, modified 1989, modified 2014]

EC 1.14.15.5

Accepted name: corticosterone 18-monooxygenase

Reaction: corticosterone + 2 reduced adrenodoxin + O2 + 2 H+ = 18-hydroxycorticosterone + 2 oxidized adrenodoxin + H2O

Other name(s): corticosterone 18-hydroxylase; corticosterone methyl oxidase; corticosterone,reduced-adrenal-ferredoxin:oxygen oxidoreductase (18-hydroxylating

Systematic name: corticosterone,reduced-adrenodoxin:oxygen oxidoreductase (18-hydroxylating)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-75-0

References:

1. Raman, P.B., Sharma, D.C. and Dorfman, R.I. Studies on aldosterone biosynthesis in vitro. Biochemistry 5 (1966) 1795.

[EC 1.14.15.5 created 1972]

EC 1.14.15.6

Accepted name: cholesterol monooxygenase (side-chain-cleaving)

Reaction: cholesterol + 6 reduced adrenodoxin + 3 O2 + 6 H+ = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O

Other name(s): cholesterol desmolase; cytochrome P-450scc; C27-side chain cleavage enzyme; cholesterol 20-22-desmolase; cholesterol C20-22 desmolase; cholesterol side-chain cleavage enzyme; cholesterol side-chain-cleaving enzyme; steroid 20-22 desmolase; steroid 20-22-lyase; CYP11A1 (gene name)

Systematic name: cholesterol,reduced-adrenodoxin:oxygen oxidoreductase (side-chain-cleaving)

Comments: A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37292-81-2, 440354-98-3

References:

1. Burstein, S., Middleditch, B.S. and Gut, M. Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J. Biol. Chem. 250 (1975) 9028-9037. [PMID: 1238395]

2. Hanukoglu, I., Spitsberg, V., Bumpus, J.A., Dus, K.M. and Jefcoate, C.R. Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover. J. Biol. Chem. 256 (1981) 4321-4328. [PMID: 7217084]

3. Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27-31. [PMID: 3011431]

4. Strushkevich, N., MacKenzie, F., Cherkesova, T., Grabovec, I., Usanov, S. and Park, H.W. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc. Natl. Acad. Sci. USA 108 (2011) 10139-10143. [PMID: 21636783]

5. Mast, N., Annalora, A.J., Lodowski, D.T., Palczewski, K., Stout, C.D. and Pikuleva, I.A. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J. Biol. Chem. 286 (2011) 5607-5613. [PMID: 21159775]

[EC 1.14.15.6 created 1983, modified 2013, modified 2014]

EC 1.14.15.7

Accepted name: choline monooxygenase

Reaction: choline + O2 + 2 reduced ferredoxin + 2 H+ = betaine aldehyde hydrate + H2O + 2 oxidized ferredoxin

Glossary: betaine = glycine betaine = N,N,N-trimethylammonioacetate
betaine aldehyde = N,N,N-trimethyl-2-oxoethylammonium
choline = (2-hydroxyethyl)trimethylammonium

Systematic name: choline,reduced-ferredoxin:oxygen oxidoreductase

Comments: The spinach enzyme, which is located in the chloroplast, contains a Rieske-type [2Fe-2S] cluster, and probably also a mononuclear Fe centre. Requires Mg2+. Catalyses the first step of glycine betaine synthesis. In many bacteria, plants and animals, betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. Different enzymes are involved in the first reaction. In plants, the reaction is catalysed by this enzyme whereas in animals and many bacteria it is catalysed by either membrane-bound EC 1.1.99.1 (choline dehydrogenase) or soluble EC 1.1.3.17 (choline oxidase) [7]. The enzyme involved in the second step, EC 1.2.1.8 (betaine-aldehyde dehydrogenase), appears to be the same in plants, animals and bacteria. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 (glycine/sarcosine N-methyltransferase) and EC 2.1.1.157 (sarcosine/dimethylglycine N-methyltransferase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 118390-76-4

References:

1. Brouquisse, R., Weigel, P., Rhodes, D., Yocum, C.F. and Hanson, A.D. Evidence for a ferredoxin-dependent choline monooxygenase from spinach chloroplast stroma. Plant Physiol. 90 (1989) 322-329. [PMID: 16666757]

2. Burnet, M., Lafontaine, P.J. and Hanson, A.D. Assay, purification, and partial characterization of choline monooxygenase from spinach. Plant Physiol. 108 (1995) 581-588. [PMID: 12228495]

3. Rathinasabapathi, B., Burnet, M., Russell, B.L., Gage, D.A., Liao, P., Nye, G.J., Scott, P., Golbeck, J.H. and Hanson, A.D. Choline monooxygenase, an unusual iron-sulfur enzyme catalyzing the first step of glycine betaine synthesis in plants: Prosthetic group characterization and cDNA cloning. Proc. Natl. Acad. Sci. USA 94 (1997) 3454-3458. [PMID: 9096415]

4. Russell, B.L., Rathinasabapathi, B. and Hanson, A.D. Osmotic stress induces expression of choline monooxygenase in sugar beet and amaranth. Plant Physiol. 116 (1998) 859-865. [PMID: 9489025]

5. Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. Glycine betaine synthesis in transgenic tobacco expressing choline monooxygenase is limited by the endogenous choline supply. Plant J. 16 (1998) 101-110.

6. Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. The endogenous choline supply limits glycine betaine synthesis in transgenic tobacco expressing choline. Plant J. 16 (1998) 487-496. [PMID: 9881168]

7. Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932-4942. [PMID: 12466265]

[EC 1.14.15.7 created 2001, modified 2002 (EC 1.14.14.4 created 2000, incorporated 2002), modified 2005, modified 2011]

EC 1.14.15.8

Accepted name: steroid 15β-monooxygenase

Reaction: progesterone + 2 reduced [2Fe-2S] ferredoxin + O2 = 15β-hydroxyprogesterone + 2 oxidized [2Fe-2S] ferredoxin + H2O

Other name(s): cytochrome P-450meg; cytochrome P450meg; steroid 15β-hydroxylase; CYP106A2; BmCYP106A2

Systematic name: progesterone,reduced-ferredoxin:oxygen oxidoreductase (15β-hydroxylating)

Comments: The enzyme from Bacillus megaterium hydroxylates a variety of 3-oxo-Δ4-steroids in position 15β. Ring A-reduced, aromatic, and 3β-hydroxy-Δ4-steroids do not serve as substrates [2].

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

References:

1. Berg, A., Ingelman-Sundberg, M. and Gustafsson, J.A. Purification and characterization of cytochrome P-450meg. J. Biol. Chem. 254 (1979) 5264-5271. [PMID: 109432]

2. Berg, A., Gustafsson, J.A. and Ingelman-Sundberg, M. Characterization of a cytochrome P-450-dependent steroid hydroxylase system present in Bacillus megaterium. J. Biol. Chem. 251 (1976) 2831-2838. [PMID: 177422]

3. Lisurek, M., Kang, M.J., Hartmann, R.W. and Bernhardt, R. Identification of monohydroxy progesterones produced by CYP106A2 using comparative HPLC and electrospray ionisation collision-induced dissociation mass spectrometry. Biochem. Biophys. Res. Commun. 319 (2004) 677-682. [PMID: 15178459]

4. Goni, G., Zollner, A., Lisurek, M., Velazquez-Campoy, A., Pinto, S., Gomez-Moreno, C., Hannemann, F., Bernhardt, R. and Medina, M. Cyanobacterial electron carrier proteins as electron donors to CYP106A2 from Bacillus megaterium ATCC 13368. Biochim. Biophys. Acta 1794 (2009) 1635-1642. [PMID: 19635596]

5. Lisurek, M., Simgen, B., Antes, I. and Bernhardt, R. Theoretical and experimental evaluation of a CYP106A2 low homology model and production of mutants with changed activity and selectivity of hydroxylation. Chembiochem 9 (2008) 1439-1449. [PMID: 18481342]

[EC 1.14.15.8 created 2010]

EC 1.14.15.9

Accepted name: spheroidene monooxygenase

Reaction: (1) spheroidene + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = spheroiden-2-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(1a) spheroidene + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2-hydroxyspheroidene + oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) 2-hydroxyspheroidene + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2,2-dihydroxyspheroidene + oxidized ferredoxin [iron-sulfur] cluster + H2O
(1c) 2,2-dihydroxyspheroidene = spheroiden-2-one + H2O (spontaneous)
(2) spirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = 2-oxospirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(2a) spirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2-hydroxyspirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(2b) 2-hydroxyspirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2,2-dihydroxyspirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(2c) 2,2-dihydroxyspirilloxanthin = 2-oxospirilloxanthin + H2O (spontaneous)
(3) 2-oxospirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = 2,2'-dioxospirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(3a) 2-oxospirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2'-hydroxy-2-oxospirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(3b) 2'-hydroxy-2-oxospirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2',2'-dihydroxy-2-oxospirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(3c) 2',2'-dihydroxy-2-oxospirilloxanthin = 2,2'-dioxospirilloxanthin + H2O (spontaneous)

For diagram of reaction click here or click here.

Glossary: spheroidene = 3,4-didehydro-1-methoxy-1,2,7',8'-tetrahydro-ψ,ψ-carotene

Other name(s): CrtA; acyclic carotenoid 2-ketolase; spirilloxanthin monooxygenase; 2-oxo-spirilloxanthin monooxygenase

Systematic name: spheroidene,reduced-ferredoxin:oxygen oxidoreductase (spheroiden-2-one-forming)

Comments: The enzyme is involved in spheroidenone biosynthesis and in 2,2'-dioxospirilloxanthin biosynthesis. The enzyme from Rhodobacter sphaeroides contains heme at its active site [1].

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

References:

1. Lee, P.C., Holtzapple, E. and Schmidt-Dannert, C. Novel activity of Rhodobacter sphaeroides spheroidene monooxygenase CrtA expressed in Escherichia coli, Appl. Environ. Microbiol. 76 (2010) 7328-7331. [PMID: 20851979]

2. Gerjets, T., Steiger, S. and Sandmann, G. Catalytic properties of the expressed acyclic carotenoid 2-ketolases from Rhodobacter capsulatus and Rubrivivax gelatinosus, Biochim. Biophys. Acta 1791 (2009) 125-131. [PMID: 19136077]

[EC 1.14.15.9 created 2012, modified 2016]

EC 1.14.15.10

Accepted name: (+)-camphor 6-endo-hydroxylase

Reaction: (+)-camphor + reduced putidaredoxin + O2 = (+)-6-endo-hydroxycamphor + oxidized putidaredoxin + H2O

For diagram of reaction click here.

Other name(s): P450camr

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (6-endo-hydroxylating)

Comments: A cytochrome P-450 monooxygenase from the bacterium Rhodococcus sp. NCIMB 9784.

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

References:

1. Grogan, G., Roberts, G.A., Parsons, S., Turner, N.J. and Flitsch, S.L. P450camr, a cytochrome P450 catalysing the stereospecific 6-endo-hydroxylation of (1R)-(+)-camphor. Appl. Microbiol. Biotechnol. 59 (2002) 449-454. [PMID: 12172608]

[EC 1.14.15.10 created 2012]

EC 1.14.15.11

Accepted name: pentalenic acid synthase

Reaction: 1-deoxypentalenate + 2 reduced ferredoxin + O2 = pentalenate + 2 oxidized ferredoxin + H2O

For diagram of reaction click here.

Glossary: 1-deoxypentalenate = (1R,3aR,5aS,8aR)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate
pentalenate = (1R,3aR,5aS,6R,8aS)-6-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): CYP105D7; sav7469 (gene name); 1-deoxypentalenate,reduced ferredoxin:O2 oxidoreductase

Systematic name: 1-deoxypentalenate,reduced ferredoxin:oxygen oxidoreductase

Comments: A heme-thiolate enzyme (P-450). Isolated from the bacterium Streptomyces avermitilis. The product, pentalenate, is a co-metabolite from pentalenolactone biosynthesis.

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

References:

1. Takamatsu, S., Xu, L.H., Fushinobu, S., Shoun, H., Komatsu, M., Cane, D.E. and Ikeda, H. Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis. J. Antibiot. (Tokyo) 64 (2011) 65-71. [PMID: 21081950]

[EC 1.14.15.11 created 2012]

[EC 1.14.15.12 Transferred entry: pimeloyl-[acyl-carrier protein] synthase, now EC 1.14.14.46, pimeloyl-[acyl-carrier protein] synthase (EC 1.14.15.12 created 2013, deleted 2017)]

EC 1.14.15.13

Accepted name: pulcherriminic acid synthase

Reaction: cyclo(L-leucyl-L-leucyl) + 6 reduced ferredoxin + 3 O2 = pulcherriminic acid + 6 oxidized ferredoxin + 4 H2O

For diagram of reaction click here.

Glossary: cyclo(L-leucyl-L-leucyl) = (3S,6S)-3,6-bis(2-methylpropyl)piperazine-2,5-dione
pulcherriminic acid = 2,5-dihydroxy-3,6-bis(2-methylpropyl)pyrazine bis-N-oxide

Other name(s): cyclo-L-leucyl-L-leucyl dipeptide oxidase; CYP134A1; CypX (ambiguous)

Systematic name: cyclo(L-leucyl-L-leucyl),reduced-ferredoxin:oxygen oxidoreductase (N-hydroxylating,aromatizing)

Comments: A heme-thiolate (P-450) enzyme from the bacterium Bacillus subtilis. The order of events during the overall reaction is unknown. Pulcherrimic acid spontaneously forms an iron chelate with Fe(3+) to form the red pigment pulcherrimin [2].

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

References:

1. MacDonald, J.C. Biosynthesis of pulcherriminic acid. Biochem. J. 96 (1965) 533-538. [PMID: 5837792]

2. Cryle, M.J., Bell, S.G. and Schlichting, I. Structural and biochemical characterization of the cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase. Biochemistry 49 (2010) 7282-7296. [PMID: 20690619]

[EC 1.14.15.13 created 2013]

EC 1.14.15.14

Accepted name: methyl-branched lipid ω-hydroxylase

Reaction: a methyl-branched lipid + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = an ω-hydroxy-methyl-branched lipid + H2O + 2 oxidized ferredoxin [iron-sulfur] cluster

Other name(s): CYP124

Systematic name: methyl-branched lipid,reduced-ferredoxin:oxygen oxidoreductase (ω-hydroxylating)

Comments: The enzyme, found in pathogenic and nonpathogenic mycobacteria species, actinomycetes, and some proteobacteria, hydroxylates the ω-carbon of a number of methyl-branched lipids, including (2E,6E)-farnesol, phytanate, geranylgeraniol, 15-methylpalmitate and (2E,6E)-farnesyl diphosphate. It is a P-450 heme-thiolate enzyme.

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

References:

1. Johnston, J.B., Kells, P.M., Podust, L.M. and Ortiz de Montellano, P.R. Biochemical and structural characterization of CYP124: a methyl-branched lipid ω-hydroxylase from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106 (2009) 20687-20692. [PMID: 19933331]

[EC 1.14.15.14 created 2015]

EC 1.14.15.15

Accepted name: cholestanetriol 26-monooxygenase

Reaction: 5β-cholestane-3α,7α,12α-triol + 6 reduced adrenodoxin + 6 H+ + 3 O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) 5β-cholestane-3α,7α,12α-triol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 oxidized adrenodoxin + H2O
(1b) (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 oxidized adrenodoxin + 2 H2O
(1c) (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Other name(s): 5β-cholestane-3α,7α,12α-triol 26-hydroxylase; 5β-cholestane-3α,7α,12α-triol hydroxylase; cholestanetriol 26-hydroxylase; sterol 27-hydroxylase; sterol 26-hydroxylase; cholesterol 27-hydroxylase; CYP27A; CYP27A1; cytochrome P450 27A1'

Systematic name: 5β-cholestane-3α,7α,12α-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)

Comments: This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

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

References:

1. Masui, T., Herman, R. and Staple, E. The oxidation of 5β-cholestane-3α,7α,12α,26-tetraol to 5β-cholestane-3α,7α,12α-triol-26-oic acid via 5β-cholestane-3α,7α,12α-triol-26-al by rat liver. Biochim. Biophys. Acta 117 (1966) 266-268. [PMID: 5914340]

2. Okuda, K. and Hoshita, N. Oxidation of 5β-cholestane-3α,7α,12α-triol by rat-liver mitochondria. Biochim. Biophys. Acta 164 (1968) 381-388. [PMID: 4388637]

3. Wikvall, K. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C27-steroids. J. Biol. Chem. 259 (1984) 3800-3804. [PMID: 6423637]

4. Andersson, S., Davis, D.L., Dahlbäck, H., Jörnvall, H. and Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264 (1989) 8222-8229. [PMID: 2722778]

5. Dahlback, H. and Holmberg, I. Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-45026 from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 167 (1990) 391-395. [PMID: 2322231]

6. Holmberg-Betsholtz, I., Lund, E., Björkhem, I. and Wikvall, K. Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5β-cholestane-3α,7α,12α,27-tetrol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 268 (1993) 11079-11085. [PMID: 8496170]

7. Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. J. Biol. Chem. 273 (1998) 18153-18160. [PMID: 9660774]

8. Furster, C., Bergman, T. and Wikvall, K. Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 263 (1999) 663-666. [PMID: 10512735]

9. Pikuleva, I.A., Puchkaev, A. and Björkhem, I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1. Biochemistry 40 (2001) 7621-7629. [PMID: 11412116]

[EC 1.14.15.15 created 1976 as EC 1.14.13.15, modified 2005, modified 2012, transferred 2016 to EC 1.14.15.15]

EC 1.14.15.16

Accepted name: vitamin D3 24-hydroxylase

Reaction: (1) calcitriol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitetrol + 2 oxidized adrenodoxin + H2O
(2) calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = secalciferol + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Glossary: calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol
calcitetrol = 1α,24R,25-trihydroxyvitamin D3 = (1S,3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-1,3,24,25-tetrol
secalciferol = (24R)-24,25-dihydroxycalciol = 24R,25-dihydroxyvitamin D3 = (3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-3,24,25-triol

Other name(s): CYP24A1

Systematic name: calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)

Comments: This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. The enzyme can perform up to 6 rounds of hydroxylation of the substrate calcitriol leading to calcitroic acid. The human enzyme also shows 23-hydroxylating activity leading to 1,25 dihydroxyvitamin D3-26,23-lactone as end product while the mouse and rat enzymes do not. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

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

References:

1. Masuda, S., Strugnell, S.A., Knutson, J.C., St-Arnaud, R. and Jones, G. Evidence for the activation of 1α-hydroxyvitamin D2 by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1α,24-dihydroxyvitamin D2 and 1α,25-dihydroxyvitamin D2. Biochim. Biophys. Acta 1761 (2006) 221-234. [PMID: 16516540]

2. Hamamoto, H., Kusudo, T., Urushino, N., Masuno, H., Yamamoto, K., Yamada, S., Kamakura, M., Ohta, M., Inouye, K. and Sakaki, T. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol. Pharmacol. 70 (2006) 120-128. [PMID: 16617161]

3. Sakaki, T., Kagawa, N., Yamamoto, K. and Inouye, K. Metabolism of vitamin D3 by cytochromes P450. Front. Biosci. 10 (2005) 119-134. [PMID: 15574355]

4. Prosser, D.E., Kaufmann, M., O'Leary, B., Byford, V. and Jones, G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1α,25-(OH)2D3-26,23-lactone. Proc. Natl. Acad. Sci. USA 104 (2007) 12673-12678. [PMID: 17646648]

5. Kusudo, T., Sakaki, T., Abe, D., Fujishima, T., Kittaka, A., Takayama, H., Hatakeyama, S., Ohta, M. and Inouye, K. Metabolism of A-ring diastereomers of 1α,25-dihydroxyvitamin D3 by CYP24A1. Biochem. Biophys. Res. Commun. 321 (2004) 774-782. [PMID: 15358094]

6. Sawada, N., Kusudo, T., Sakaki, T., Hatakeyama, S., Hanada, M., Abe, D., Kamao, M., Okano, T., Ohta, M. and Inouye, K. Novel metabolism of 1α,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1. Biochemistry 43 (2004) 4530-4537. [PMID: 15078099]

7. Prosser, D.E. and Jones, G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29 (2004) 664-673. [PMID: 15544953]

[EC 1.14.15.16 created 2011 as EC 1.14.13.126, transferred 2016 to EC 1.14.15.16]

EC 1.14.15.17

Accepted name: pheophorbide-a oxygenase

Reaction: pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = red chlorophyll catabolite + 2 oxidized ferredoxin [iron-sulfur] cluster (overall reaction)
(1a) pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = epoxypheophorbide a + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) epoxypheophorbide a + H2O = red chlorophyll catabolite (spontaneous)

For diagram of reaction click here.

Glossary: red chlorophyll catabolite = RCC = (7S,8S,101R)-8-(2-carboxyethyl)-8,23-dihydro-17-ethyl-19-formyl-101-(methoxycarbonyl)-3,7,13,18-tetramethyl-2-vinyl-7H-10,12-ethanobiladiene-ab-1,102(21H)-dione

Other name(s): pheide a monooxygenase; pheide a oxygenase; PaO; PAO

Systematic name: pheophorbide-a,ferredoxin:oxygen oxidoreductase (biladiene-forming)

Comments: This enzyme catalyses a key reaction in chlorophyll degradation, which occurs during leaf senescence and fruit ripening in higher plants. The enzyme from Arabidopsis contains a Rieske-type iron-sulfur cluster [2] and requires reduced ferredoxin, which is generated either by NADPH through the pentose-phosphate pathway or by the action of photosystem I [4]. While still attached to this enzyme, the product is rapidly converted into primary fluorescent chlorophyll catabolite by the action of EC 1.3.7.12, red chlorophyll catabolite reductase [2,6]. Pheophorbide b acts as an inhibitor. In 18O2 labelling experiments, only the aldehyde oxygen is labelled, suggesting that the other oxygen atom may originate from H2O [1].

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

References:

1. Hörtensteiner, S., Wüthrich, K.L., Matile, P., Ongania, K.H. and Kräutler, B. The key step in chlorophyll breakdown in higher plants. Cleavage of pheophorbide a macrocycle by a monooxygenase. J. Biol. Chem. 273 (1998) 15335-15339. [PMID: 9624113]

2. Pružinská, A., Tanner, G., Anders, I., Roca, M. and Hörtensteiner, S. Chlorophyll breakdown: pheophorbide a oxygenase is a Rieske-type iron-sulfur protein, encoded by the accelerated cell death 1 gene. Proc. Natl. Acad. Sci. USA 100 (2003) 15259-15264. [PMID: 14657372]

3. Chung, D.W., Pružinská, A., Hörtensteiner, S. and Ort, D.R. The role of pheophorbide a oxygenase expression and activity in the canola green seed problem. Plant Physiol. 142 (2006) 88-97. [PMID: 16844830]

4. Rodoni, S., Mühlecker, W., Anderl, M., Kräutler, B., Moser, D., Thomas, H., Matile, P. and Hörtensteiner, S. Chlorophyll breakdown in senescent chloroplasts. Cleavage of pheophorbide a in two enzymic steps. Plant Physiol. 115 (1997) 669-676. [PMID: 12223835]

5. Hörtensteiner, S. Chlorophyll degradation during senescence. Annu. Rev. Plant Biol. 57 (2006) 55-77. [PMID: 16669755]

6. Pružinská, A., Anders, I., Aubry, S., Schenk, N., Tapernoux-Lüthi, E., Müller, T., Kräutler, B. and Hörtensteiner, S. In vivo participation of red chlorophyll catabolite reductase in chlorophyll breakdown. Plant Cell 19 (2007) 369-387. [PMID: 17237353]

[EC 1.14.15.17 created 2007 as EC 1.14.12.20, transferred 2016 to EC 1.14.15.17]

EC 1.14.15.18

Accepted name: calcidiol 1-monooxygenase

Reaction: calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitriol + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Glossary: calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol

Other name(s): 25-hydroxycholecalciferol 1-hydroxylase; 25-hydroxycholecalciferol 1-monooxygenase; 1-hydroxylase-25-hydroxyvitamin D3; 25-hydroxy D3-1α-hydroxylase; 25-hydroxycholecalciferol 1α-hydroxylase; 25-hydroxyvitamin D3 1α-hydroxylase

Systematic name: calcidiol,adrenodoxin:oxygen oxidoreductase (1-hydroxylating)

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

References:

1. Gray, R.W., Omdahl, J.L., Ghazarian, J.G. and De Luca, H.F. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J. Biol. Chem. 247 (1972) 7528-7532. [PMID: 4404596]

[EC 1.14.15.18 created 1976 as EC 1.14.13.13, transferred 2016 to EC 1.14.15.18]

EC 1.14.15.19

Accepted name: C-19 steroid 1α-hydroxylase

Reaction: testosterone + 2 reduced ferredoxin [iron-sulfur] cluster + O2 + 2 H+ = 1α-hydroxytestosterone + H2O + 2 oxidized ferredoxin [iron-sulfur] cluster

Other name(s): CYP260A1

Systematic name: testosterone,reduced-ferredoxin:oxygen oxidoreductase (1α-hydroxylating)

Comments: The enzyme, characterized from the bacterium Sorangium cellulosum, is a class I cytochrome P-450, and uses ferredoxin as its electron donor [1]. It was shown to act on several C-19 steroid substrates, including testosterone, androstenedione, testosterone-acetate and 11-oxoandrostenedione [2].

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

References:

1. Ewen, K.M., Hannemann, F., Khatri, Y., Perlova, O., Kappl, R., Krug, D., Huttermann, J., Muller, R. and Bernhardt, R. Genome mining in Sorangium cellulosum So ce56: identification and characterization of the homologous electron transfer proteins of a myxobacterial cytochrome P450. J. Biol. Chem. 284 (2009) 28590-28598. [PMID: 19696019]

2. Khatri, Y., Ringle, M., Lisurek, M., von Kries, J.P., Zapp, J. and Bernhardt, R. Substrate hunting for the myxobacterial CYP260A1 revealed new 1α-hydroxylated products from C-19 steroids. Chembiochem 17 (2016) 90-101. [PMID: 26478560]

[EC 1.14.15.19 created 2016]

EC 1.14.15.20

Accepted name: heme oxygenase (biliverdin-producing, ferredoxin)

Reaction: protoheme + 6 reduced ferredoxin [iron-sulfur] cluster + 3 O2 + 6 H+ = biliverdin + Fe2+ + CO + 6 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O

For diagram of reaction click here.

Other name(s): HO1 (gene name); HY1 (gene name); HO3 (gene name); HO4 (gene name); pbsA1 (gene name)

Systematic name: protoheme,reduced ferredoxin:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Comments: The enzyme, found in plants, algae, and cyanobacteria, participates in the biosynthesis of phytochromobilin and phytobilins. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules. The third oxygen molecule provides the oxygen atom that converts the α-carbon to CO. Unlike this enzyme, which uses ferredoxin as its electron donor, the electron source for the related mammalian enzyme (EC 1.14.14.18) is EC 1.6.2.4, NADPH—hemoprotein reductase.

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

References:

1. Montgomery, B.L. and Lagarias, J.C. Phytochrome ancestry: sensors of bilins and light. Trends Plant Sci 7 (2002) 357-366. [PMID: 12167331]

2. Sugishima, M., Migita, C.T., Zhang, X., Yoshida, T. and Fukuyama, K. Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC 6803 in complex with heme. Eur. J. Biochem. 271 (2004) 4517-4525. [PMID: 15560792]

3. Dammeyer, T. and Frankenberg-Dinkel, N. Function and distribution of bilin biosynthesis enzymes in photosynthetic organisms. Photochem Photobiol Sci 7 (2008) 1121-1130. [PMID: 18846276]

[EC 1.14.15.20 created 2016]

EC 1.14.15.21

Accepted name: zeaxanthin epoxidase

Reaction: zeaxanthin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = violaxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O (overall reaction)
(1a) zeaxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = antheraxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) antheraxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = violaxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Other name(s): Zea-epoxidase

Systematic name: zeaxanthin,reduced ferredoxin:oxygen oxidoreductase

Comments: A flavoprotein (FAD) that is active under conditions of low light. Along with EC 1.23.5.1, violaxanthin de-epoxidase, this enzyme forms part of the xanthophyll (or violaxanthin) cycle, which is involved in protecting the plant against damage by excess light. It will also epoxidize lutein in some higher-plant species.

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

References:

1. Buch, K., Stransky, H. and Hager, A. FAD is a further essential cofactor of the NAD(P)H and O2-dependent zeaxanthin-epoxidase. FEBS Lett. 376 (1995) 45-48. [PMID: 8521963]

2. Bugos, R.C., Hieber, A.D. and Yamamoto, H.Y. Xanthophyll cycle enzymes are members of the lipocalin family, the first identified from plants. J. Biol. Chem. 273 (1998) 15321-15324. [PMID: 9624110]

3. Thompson, A.J., Jackson, A.C., Parker, R.A., Morpeth, D.R., Burbidge, A. and Taylor, I.B. Abscisic acid biosynthesis in tomato: regulation of zeaxanthin epoxidase and 9-cis-epoxycarotenoid dioxygenase mRNAs by light/dark cycles, water stress and abscisic acid. Plant Mol. Biol. 42 (2000) 833-845. [PMID: 10890531]

4. Hieber, A.D., Bugos, R.C. and Yamamoto, H.Y. Plant lipocalins: violaxanthin de-epoxidase and zeaxanthin epoxidase. Biochim. Biophys. Acta 1482 (2000) 84-91. [PMID: 11058750]

5. Frommolt, R., Goss, R. and Wilhelm, C. The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae) exhibit different substrate-specific reaction kinetics compared to spinach. Planta 213 (2001) 446-456. [PMID: 11506368]

6. Frommolt, R., Goss, R. and Wilhelm, C. (Erratum Report.) The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae) exhibit different substrate-specific reaction kinetics compared to spinach. Planta 213 (2001) 492. [PMID: 11506368]

7. Matsubara, S., Morosinotto, T., Bassi, R., Christian, A.L., Fischer-Schliebs, E., Luttge, U., Orthen, B., Franco, A.C., Scarano, F.R., Forster, B., Pogson, B.J. and Osmond, C.B. Occurrence of the lutein-epoxide cycle in mistletoes of the Loranthaceae and Viscaceae. Planta 217 (2003) 868-879. [PMID: 12844265]

[EC 1.14.15.21 created 2005 as EC 1.14.13.90, transferred 2016 to EC 1.14.15.21]

EC 1.14.15.22

Accepted name: vitamin D 1,25-hydroxylase

Reaction: (1) calciol + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = calcidiol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(2) calcidiol + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = calcitriol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: calciol = cholecalciferol = vitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol

Other name(s): CYP105A1; Streptomyces griseolus cytochrome P450SU-1

Systematic name: calciol,ferredoxin:oxygen oxidoreductase (1,25-hydroxylating)

Comments: A P-450 (heme-thiolate) enzyme found in the bacterium Streptomyces griseolus. cf. EC 1.14.14.24, vitamin D 25-hydroxylase and EC 1.14.15.18, calcidiol 1-monooxygenase.

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

References:

1. Sawada, N., Sakaki, T., Yoneda, S., Kusudo, T., Shinkyo, R., Ohta, M. and Inouye, K. Conversion of vitamin D3 to 1α,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem. Biophys. Res. Commun. 320 (2004) 156-164. [PMID: 15207715]

2. Sugimoto, H., Shinkyo, R., Hayashi, K., Yoneda, S., Yamada, M., Kamakura, M., Ikushiro, S., Shiro, Y. and Sakaki, T. Crystal structure of CYP105A1 (P450SU-1) in complex with 1α,25-dihydroxyvitamin D3. Biochemistry 47 (2008) 4017-4027. [PMID: 18314962]

[EC 1.14.15.22 created 2016]

EC 1.14.15.23

Accepted name: chloroacetanilide N-alkylformylase

Reaction: butachlor + 2 reduced ferredoxin [iron-sulfur] cluster + O2 = 2-chloro-N-(2,6-diethylphenyl)acetamide + butyl formate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: butachlor = N-(butoxymethyl)-2-chloro-N-(2,6-diethylphenyl)acetamide
acetochlor = N-(ethoxymethyl)-2-chloro-N-(2-ethyl,6-methylphenyl)acetamide
alachlor = N-(methoxymethyl)-2-chloro-N-(2,6-diethylphenyl)acetamide

Other name(s): cndA (gene name)

Systematic name: butachlor,ferredoxin:oxygen oxidoreductase (butyl formate-releasing)

Comments: The enzyme, characterized from the bacterium Sphingomonas sp. DC-6, initiates the degradation of several chloroacetanilide herbicides, including alachlor, acetochlor, and butachlor. The enzyme is a Rieske non-heme iron oxygenase, and requires a ferredoxin and EC 1.18.1.3, ferredoxin-NAD+ reductase, for activity.

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

References:

1. Chen, Q., Wang, C.H., Deng, S.K., Wu, Y.D., Li, Y., Yao, L., Jiang, J.D., Yan, X., He, J. and Li, S.P. Novel three-component Rieske non-heme iron oxygenase system catalyzing the N-dealkylation of chloroacetanilide herbicides in sphingomonads DC-6 and DC-2. Appl. Environ. Microbiol. 80 (2014) 5078-5085. [PMID: 24928877]

[EC 1.14.15.23 created 2017]

EC 1.14.15.24

Accepted name: β-carotene 3-hydroxylase

Reaction: β-carotene + 4 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2 = zeaxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O (overall reaction)
(1a) β-carotene + 2 reduced ferredoxin [iron-sulfur] cluster + H+ + O2 = β-cryptoxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) β-cryptoxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + H+ + O2 = zeaxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here or click here

Other name(s): β-carotene 3,3'-monooxygenase; CrtZ

Systematic name: β-carotene,reduced ferredoxin [iron-sulfur] cluster:oxygen 3-oxidoreductase

Comments: Requires ferredoxin and Fe(II). Also acts on other carotenoids with a β-end group. In some species canthaxanthin is the preferred substrate.

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

References:

1. Sun, Z., Gantt, E. and Cunningham, F.X., Jr. Cloning and functional analysis of the β-carotene hydroxylase of Arabidopsis thaliana. J. Biol. Chem. 271 (1996) 24349-24352. [PMID: 8798688]

2. Fraser, P.D., Miura, Y. and Misawa, N. In vitro characterization of astaxanthin biosynthetic enzymes. J. Biol. Chem. 272 (1997) 6128-6135. [PMID: 9045623]

3. Fraser, P.D., Shimada, H. and Misawa, N. Enzymic confirmation of reactions involved in routes to astaxanthin formation, elucidated using a direct substrate in vitro assay. Eur. J. Biochem. 252 (1998) 229-236. [PMID: 9523693]

4. Bouvier, F., Keller, Y., d'Harlingue, A. and Camara, B. Xanthophyll biosynthesis: molecular and functional characterization of carotenoid hydroxylases from pepper fruits (Capsicum annuum L.). Biochim. Biophys. Acta 1391 (1998) 320-328. [PMID: 9555077]

5. Linden, H. Carotenoid hydroxylase from Haematococcus pluvialis: cDNA sequence, regulation and functional complementation. Biochim. Biophys. Acta 1446 (1999) 203-212. [PMID: 10524195]

6. Zhu, C., Yamamura, S., Nishihara, M., Koiwa, H. and Sandmann, G. cDNAs for the synthesis of cyclic carotenoids in petals of Gentiana lutea and their regulation during flower development. Biochim. Biophys. Acta 1625 (2003) 305-308. [PMID: 12591618]

7. Choi, S.K., Matsuda, S., Hoshino, T., Peng, X. and Misawa, N. Characterization of bacterial β-carotene 3,3'-hydroxylases, CrtZ, and P450 in astaxanthin biosynthetic pathway and adonirubin production by gene combination in Escherichia coli. Appl. Microbiol. Biotechnol. 72 (2006) 1238-1246. [PMID: 16614859]

[EC 1.14.15.24 created 2011 as EC 1.14.13.129, transferred 2017 to EC 1.14.15.24]

EC 1.14.15.25

Accepted name: p-cymene methyl-monooxygenase

Reaction: p-cymene + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = 4-isopropylbenzyl alcohol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: p-cymene = 4-methyl-1-(propan-2-yl)benzene

Other name(s): cymAa (gene name); cymA (gene name); p-cymene methyl hydroxylase

Systematic name: p-cymene,ferredoxin:oxygen oxidoreductase (methyl-hydroxylating)

Comments: The enzyme, characterized from several Pseudomonas strains, initiates p-cymene catabolism through hydroxylation of the methyl group. The enzyme has a distinct preference for substrates containing at least an alkyl or heteroatom substituent at the para-position of toluene. The electrons are provided by a reductase (EC 1.18.1.3, ferredoxin—NAD+ reductase) that transfers electrons from NADH via FAD and an [2Fe-2S] cluster. In Pseudomonas chlororaphis the presence of a third component of unknown function greatly increases the activity. cf. EC 1.14.15.26, toluene methyl-monooxygenase.

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

References:

1. Eaton, R.W. p-Cymene catabolic pathway in Pseudomonas putida F1: cloning and characterization of DNA encoding conversion of p-cymene to p-cumate. J. Bacteriol. 179 (1997) 3171-3180. [PMID: 9150211]

2. Dutta, T.K. and Gunsalus, I.C. Reductase gene sequences and protein structures: p-cymene methyl hydroxylase. Biochem. Biophys. Res. Commun. 233 (1997) 502-506. [PMID: 9144566]

3. Nishio, T., Patel, A., Wang, Y. and Lau, P.C. Biotransformations catalyzed by cloned p-cymene monooxygenase from Pseudomonas putida F1. Appl. Microbiol. Biotechnol. 55 (2001) 321-325. [PMID: 11341314]

4. Dutta, T.K., Chakraborty, J., Roy, M., Ghosal, D., Khara, P. and Gunsalus, I.C. Cloning and characterization of a p-cymene monooxygenase from Pseudomonas chlororaphis subsp. aureofaciens. Res. Microbiol. 161 (2010) 876-882. [PMID: 21035544]

[EC 1.14.15.25 created 2018]

EC 1.14.15.26

Accepted name: toluene methyl-monooxygenase

Reaction: (1) toluene + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = benzyl alcohol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(2) p-xylene + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = 4-methylbenzyl alcohol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(3) m-xylene + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = 3-methylbenzyl alcohol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: toluene = methylbenzene
p-xylene = 1,4-dimethylbenzene
m-xylene = 1,3-dimethylbenzene

Other name(s): xylM (gene names); ntnM (gene names)

Systematic name: methylbenzene,ferredoxin:oxygen oxidoreductase (methyl-hydroxylating)

Comments: The enzyme, characterized from several Pseudomonas strains, catalyses the first step in the degradation of toluenes and xylenes. It has a broad substrate specificity and is also active with substituted compounds, such as chlorotoluenes. The electrons are provided by a reductase (EC 1.18.1.3, ferredoxin—NAD+ reductase) that transfers electrons from NADH via FAD and an [2Fe-2S] cluster. The enzyme can also act on its products, producing gem-diols that spontaneously dehydrate to form aldehydes.

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

References:

1. Suzuki, M., Hayakawa, T., Shaw, J.P., Rekik, M. and Harayama, S. Primary structure of xylene monooxygenase: similarities to and differences from the alkane hydroxylation system. J. Bacteriol. 173 (1991) 1690-1695. [PMID: 1999388]

2. Shaw, J.P. and Harayama, S. Purification and characterisation of the NADH:acceptor reductase component of xylene monooxygenase encoded by the TOL plasmid pWW0 of Pseudomonas putida mt-2. Eur. J. Biochem. 209 (1992) 51-61. [PMID: 1327782]

3. Brinkmann, U. and Reineke, W. Degradation of chlorotoluenes by in vivo constructed hybrid strains: problems of enzyme specificity, induction and prevention of meta-pathway. FEMS Microbiol. Lett. 75 (1992) 81-87. [PMID: 1526468]

4. James, K.D. and Williams, P.A. ntn genes determining the early steps in the divergent catabolism of 4-nitrotoluene and toluene in Pseudomonas sp. strain TW3. J. Bacteriol. 180 (1998) 2043-2049. [PMID: 9555884]

[EC 1.14.15.26 created 2018]

EC 1.14.15.27

Accepted name: β-dihydromenaquinone-9 ω-hydroxylase

Reaction: β-dihydromenaquinone-9 + 2 reduced ferredoxin [iron-sulfur] cluster + O2 = ω-hydroxy-β-dihydromenaquinone-9 + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Glossary: β-dihydromenaquinone-9 = MK-9(II-H2) = 2-methyl-3-[(2E,10E,14E,18E,22E,26E,30E,33E)-3,7,11,15,19,23,27,31,35-nonamethylhexatriaconta-2,10,14,18,22,26,30,33-octaen-1-yl]naphthalene-1,4-dione

Other name(s): cyp128 (gene name)

Systematic name: β-dihydromenaquinone-9,reduced ferredoxin:oxygen oxidoreductase (ω-hydroxylating)

Comments: The bacterial cytochrome P-450 enzyme is involved in the biosynthesis of ω-sulfo-β-dihydromenaquinone-9 by members of the Mycobacterium tuberculosis complex.

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

References:

1. Holsclaw, C.M., Sogi, K.M., Gilmore, S.A., Schelle, M.W., Leavell, M.D., Bertozzi, C.R. and Leary, J.A. Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis. ACS Chem. Biol. 3 (2008) 619-624. [PMID: 18928249]

2. Sogi, K.M., Holsclaw, C.M., Fragiadakis, G.K., Nomura, D.K., Leary, J.A. and Bertozzi, C.R. Biosynthesis and regulation of sulfomenaquinone, a metabolite associated with virulence in Mycobacterium tuberculosis. ACS Infect Dis 2 (2016) 800-806. [PMID: 27933784]

[EC 1.14.15.27 created 2018]

EC 1.14.15.28

Accepted name: cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]

Reaction: cholest-4-en-3-one + 6 reduced [2Fe-2S] ferredoxin + 3 O2 = (25R)-3-oxocholest-4-en-26-oate + 6 oxidized [2Fe-2S] ferredoxin + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-hydroxycholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + H2O
(1b) (25R)-26-hydroxycholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-oxocholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + 2 H2O
(1c) (25R)-26-oxocholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-3-oxocholest-4-en-26-oate + 2 oxidized [2Fe-2S] ferredoxin + H2O

Other name(s): CYP142

Systematic name: cholest-4-en-3-one,reduced [2Fe-2S] ferredoxin:oxygen oxidoreductase [(25R)-3-oxocholest-4-en-26-oate forming]

Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in several bacterial pathogens, is involved in degradation of the host cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol. The products are exclusively in the (25R) conformation. The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.29, cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]. The enzyme can receive electrons from ferredoxin reductase in vitro, its natural electron donor is not known yet.

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

References:

1. Driscoll, M.D., McLean, K.J., Levy, C., Mast, N., Pikuleva, I.A., Lafite, P., Rigby, S.E., Leys, D. and Munro, A.W. Structural and biochemical characterization of Mycobacterium tuberculosis CYP142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen. J. Biol. Chem. 285 (2010) 38270-38282. [PMID: 20889498]

2. Johnston, J.B., Ouellet, H. and Ortiz de Montellano, P.R. Functional redundancy of steroid C26-monooxygenase activity in Mycobacterium tuberculosis revealed by biochemical and genetic analyses. J. Biol. Chem. 285 (2010) 36352-36360. [PMID: 20843794]

[EC 1.14.15.28 created 2016 as EC 1.14.13.221, transferred 2018 to EC 1.14.15.28]

EC 1.14.15.29

Accepted name: cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]

Reaction: cholest-4-en-3-one + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 = (25S)-3-oxocholest-4-en-26-oate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-hydroxycholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) (25S)-26-hydroxycholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-oxocholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(1c) (25S)-26-oxocholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-3-oxocholest-4-en-26-oate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Other name(s): CYP125; CYP125A1; cholest-4-en-3-one 27-monooxygenase (misleading); cholest-4-en-3-one,NADH:oxygen oxidoreductase (26-hydroxylating); cholest-4-en-3-one 26-monooxygenase (ambiguous)

Systematic name: cholest-4-en-3-one,[reduced ferredoxin]:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]

Comments: A cytochrome P-450 (heme-thiolate) protein found in several bacterial pathogens. The enzyme is involved in degradation of the host’s cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol [4]. The products are exclusively in the (25S) configuration. The enzyme is part of a two-component system that also includes a ferredoxin reductase (most likely KshB, which also interacts with EC 1.14.15.30, 3-ketosteroid 9α-monooxygenase). The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.28, cholest-4-en-3-one 27-monooxygenase.

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

References:

1. Rosloniec, K.Z., Wilbrink, M.H., Capyk, J.K., Mohn, W.W., Ostendorf, M., van der Geize, R., Dijkhuizen, L. and Eltis, L.D. Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1. Mol. Microbiol. 74 (2009) 1031-1043. [PMID: 19843222]

2. McLean, K.J., Lafite, P., Levy, C., Cheesman, M.R., Mast, N., Pikuleva, I.A., Leys, D. and Munro, A.W. The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection. J. Biol. Chem. 284 (2009) 35524-35533. [PMID: 19846552]

3. Capyk, J.K., Kalscheuer, R., Stewart, G.R., Liu, J., Kwon, H., Zhao, R., Okamoto, S., Jacobs, W.R., Jr., Eltis, L.D. and Mohn, W.W. Mycobacterial cytochrome P450 125 (Cyp125) catalyzes the terminal hydroxylation of C27 steroids. J. Biol. Chem. 284 (2009) 35534-35542. [PMID: 19846551]

4. Ouellet, H., Guan, S., Johnston, J.B., Chow, E.D., Kells, P.M., Burlingame, A.L., Cox, J.S., Podust, L.M. and de Montellano, P.R. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol. Microbiol. 77 (2010) 730-742. [PMID: 20545858]

[EC 1.14.15.29 created 2012 as EC 1.14.13.141, modified 2016, transferred 2018 to EC 1.14.15.29]

EC 1.14.15.30

Accepted name: 3-ketosteroid 9α-monooxygenase

Reaction: androsta-1,4-diene-3,17-dione + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = 9α-hydroxyandrosta-1,4-diene-3,17-dione + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Other name(s): KshA; 3-ketosteroid 9α-hydroxylase

Systematic name: androsta-1,4-diene-3,17-dione,[reduced ferredoxin]:oxygen oxidoreductase (9α-hydroxylating)

Comments: The enzyme is involved in the cholesterol degradation pathway of several bacterial pathogens, such as Mycobacterium tuberculosis. It forms a two-component system with a ferredoxin reductase (KshB). The enzyme contains a Rieske-type iron-sulfur center and non-heme iron. The product of the enzyme is unstable, and spontaneously converts to 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione.

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

References:

1. Petrusma, M., Dijkhuizen, L. and van der Geize, R. Rhodococcus rhodochrous DSM 43269 3-ketosteroid 9α-hydroxylase, a two-component iron-sulfur-containing monooxygenase with subtle steroid substrate specificity. Appl. Environ. Microbiol. 75 (2009) 5300-5307. [PMID: 19561185]

2. Capyk, J.K., D'Angelo, I., Strynadka, N.C. and Eltis, L.D. Characterization of 3-ketosteroid 9α-hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis. J. Biol. Chem. 284 (2009) 9937-9946. [PMID: 19234303]

3. Capyk, J.K., Casabon, I., Gruninger, R., Strynadka, N.C. and Eltis, L.D. Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis. J. Biol. Chem. 286 (2011) 40717-40724. [PMID: 21987574]

[EC 1.14.15.30 created 2012 as EC 1.14.13.142, transferred 2018 to EC 1.14.15.30]

EC 1.14.15.31

Accepted name: 2-hydroxy-5-methyl-1-naphthoate 7-hydroxylase

Reaction: 2-hydroxy-5-methyl-1-naphthoate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = 2,7-dihydroxy-5-methyl-1-naphthoate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Other name(s): NcsB3

Systematic name: 2-hydroxy-5-methyl-1-naphthoate,reduced ferredoxin:oxygen oxidoreductase (7-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein involved in the synthesis of neocarzinostatin in the bacterium Streptomyces carzinostaticus.

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

References:

1. Hang, V.T.T., Oh, T.J., Yamaguchi, T. and Sohng, J.K. In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore. FEMS Microbiol. Lett. 311 (2010) 119-125. [PMID: 20735485]

[EC 1.14.15.31 created 2014 as EC 1.14.99.49, transferred 2018 to EC 1.14.15.31]

EC 1.14.15.32

Accepted name: pentalenene oxygenase

Reaction: pentalenene + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = pentalen-13-al + 4 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(1a) pentalenene + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pentalen-13-ol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) pentalen-13-ol + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pentalen-13-al + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O

For diagram of reaction click here.

Other name(s): PtlI

Systematic name: pentalenene,reduced ferredoxin:oxygen 13-oxidoreductase

Comments: A cytochrome P-450 (heme-thiolate) protein found in the bacterium Streptomyces avermitilis. The enzyme is involved in the biosynthesis of pentalenolactone and related antibiotics.

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

References:

1. Quaderer, R., Omura, S., Ikeda, H. and Cane, D.E. Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlI, a cytochrome P450 of Streptomyces avermitilis. J. Am. Chem. Soc. 128 (2006) 13036-13037. [PMID: 17017767]

[EC 1.14.15.32 created 2011 as EC 1.14.13.133, transferred 2018 to EC 1.14.15.32]

EC 1.14.15.33

Accepted name: pikromycin synthase

Reaction: (1) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(2) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(3) narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novapikromyin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(4) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(5) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(6) 10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O

For diagram of reaction click here or click here.

Other name(s): PikC; CYP107L1

Systematic name: narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming)

Comments: A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit. With narbomycin it hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin. With 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin.

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

References:

1. Xue, Y., Wilson, D., Zhao, L., Liu Hw and Sherman, D.H. Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae. Chem. Biol. 5 (1998) 661-667. [PMID: 9831532]

2. Sherman, D.H., Li, S., Yermalitskaya, L.V., Kim, Y., Smith, J.A., Waterman, M.R. and Podust, L.M. The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae. J. Biol. Chem. 281 (2006) 26289-26297. [PMID: 16825192]

3. Li, S., Ouellet, H., Sherman, D.H. and Podust, L.M. Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. J. Biol. Chem. 284 (2009) 5723-5730. [PMID: 19124459]

[EC 1.14.15.33 created 2014 as EC 1.14.13.185, transferred 2018 to EC 1.14.15.33]

EC 1.14.15.34

Accepted name: 20-oxo-5-O-mycaminosyltylactone 23-monooxygenase

Reaction: 20-oxo-5-O-β-mycaminosyltylactone + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = 5-O-β-mycaminosyltylonolide + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Glossary: tylactone = (4R,5S,6S,7S,9R,11E,13E,15S,16R)-7,16-diethyl-4,6-dihydroxy-5,9,13,15-tetramethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
α-D-mycaminose = 3-dimethylamino-3,6-dideoxy-α-D-glucopyranose
tylonolide = 2-[(4R,5S,6S,7R,9R,11E,13E,15R,16R)-16-ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde

Other name(s): tylH1 (gene name)

Systematic name: 20-oxo-5-O-β-mycaminosyltylactone,reduced ferredoxin:oxygen oxidoreductase (23-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthetic pathway of the macrolide antibiotic tylosin, which is produced by several species of Streptomyces bacteria.

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

References:

1. Baltz, R.H. and Seno, E.T. Properties of Streptomyces fradiae mutants blocked in biosynthesis of the macrolide antibiotic tylosin. Antimicrob. Agents Chemother. 20 (1981) 214-225. [PMID: 7283418]

2. Reeves, C.D., Ward, S.L., Revill, W.P., Suzuki, H., Marcus, M., Petrakovsky, O.V., Marquez, S., Fu, H., Dong, S.D. and Katz, L. Production of hybrid 16-membered macrolides by expressing combinations of polyketide synthase genes in engineered Streptomyces fradiae hosts. Chem. Biol. 11 (2004) 1465-1472. [PMID: 15489173]

[EC 1.14.15.34 created 2014 as EC 1.14.13.186, transferred 2018 to EC 1.14.15.34]

EC 1.14.15.35

Accepted name: 6-deoxyerythronolide B hydroxylase

Reaction: 6-deoxyerythronolide B + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = erythronolide B + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Other name(s): DEB hydroxylase; eryF (gene name); P450(eryF); CYP107A1

Systematic name: 6-deoxyerythronolide-B,reduced ferredoxin:oxygen oxidoreductase

Comments: A cytochrome P-450 (heme-thiolate) protein isolated from the bacterium Saccharopolyspora erythraea. The enzyme is involved in the biosynthesis of the antibiotic erythromycin.

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

References:

1. Weber, J.M., Leung, J.O., Swanson, S.J., Idler, K.B. and McAlpine, J.B. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science 252 (1991) 114-117. [PMID: 2011746]

2. Shafiee, A. and Hutchinson, C.R. Macrolide antibiotic biosynthesis: isolation and properties of two forms of 6-deoxyerythronolide B hydroxylase from Saccharopolyspora erythraea (Streptomyces erythreus). Biochemistry 26 (1987) 6204-6210. [PMID: 2446657]

3. Cupp-Vickery, J.R., Li, H. and Poulos, T.L. Preliminary crystallographic analysis of an enzyme involved in erythromycin biosynthesis: cytochrome P450eryF. Proteins: Struct., Funct., Bioinf. 20 (1994) 197-201. [PMID: 7846029]

4. Nagano, S., Cupp-Vickery, J.R. and Poulos, T.L. Crystal structures of the ferrous dioxygen complex of wild-type cytochrome P450eryF and its mutants, A245S and A245T: investigation of the proton transfer system in P450eryF. J. Biol. Chem. 280 (2005) 22102-22107. [PMID: 15824115]

[EC 1.14.15.35 created 2014 as EC 1.14.13.188, transferred 2018 to EC 1.14.15.35]


EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.16.1 phenylalanine 4-monooxygenase
EC 1.14.16.2 tyrosine 3-monooxygenase
EC 1.14.16.3 anthranilate 3-monooxygenase
EC 1.14.16.4 tryptophan 5-monooxygenase
EC 1.14.16.5 alkylglycerol monooxygenase
EC 1.14.16.6 mandelate 4-monooxygenase

EC 1.14.16.7 phenylalanine 3-monooxygenase


EC 1.14.16.1

Accepted name: phenylalanine 4-monooxygenase

Reaction: L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin

For diagram click here and here also for mechanism.

Other name(s): phenylalaninase; phenylalanine 4-hydroxylase; phenylalanine hydroxylase

Systematic name: L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, 6,7-dihydropteridine reductase, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9029-73-6

References:

1. Guroff, G. and Rhoads, C.A. Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor. J. Biol. Chem. 244 (1969) 142-146. [PMID: 5773277]

2. Kaufman, S. Studies on the mechanism of the enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 234 (1959) 2677-2682.

3. Mitoma, C. Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. Biophys. 60 (1956) 476-484.

4. Udenfriend, S. and Cooper, J.R. The enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 194 (1952) 503-511.

5. Carr, R.T., Balasubramanian, S., Hawkins, P.C. and Benkovic, S.J. Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. Biochemistry 34 (1995) 7525-7532. [PMID: 7779797]

6. Andersen, O.A., Flatmark, T. and Hough, E. High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J. Mol. Biol. 314 (2001) 266-278. [PMID: 11718561]

7. Erlandsen, H., Kim, J.Y., Patch, M.G., Han, A., Volner, A., Abu-Omar, M.M. and Stevens, R.C. Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates. J. Mol. Biol. 320 (2002) 645-661. [PMID: 12096915]

[EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003]

EC 1.14.16.2

Accepted name: tyrosine 3-monooxygenase

Reaction: L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin

For diagram click here and here.

Glossary: L-dopa = 3,4-dihydroxy-L-phenylalanine

Other name(s): L-tyrosine hydroxylase; tyrosine 3-hydroxylase; tyrosine hydroxylase

Systematic name: L-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA caboxylase]kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9036-22-0

References:

1. El Mestikawy, S., Glowinski, J. and Hamon, M. Tyrosine hydroxylase activation in depolarized dopaminergic terminals -involvement of Ca2+-dependent phosphorylation. Nature (Lond.) 302 (1983) 830-832. [PMID: 6133218]

2. Ikeda, M., Levitt, M. and Udenfriend, S. Phenylalanine as substrate and inhibitor of tyrosine hydroxylase. Arch. Biochem. Biophys. 120 (1967) 420-427. [PMID: 6033458]

3. Nagatsu, T., Levitt, M. and Udenfriend, S. Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239 (1964) 2910-2917.

4. Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification of tyrosine-hydroxylase from rat pheochromocytoma, with a protein-kinase activity. C.R. Acad. Sci. Paris, Ser. 3, 302 (1986) 435-438. [PMID: 2872947]

5. Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F. and Stevens, R.C. Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Nat. Struct. Biol. 4 (1997) 578-585. [PMID: 9228951]

[EC 1.14.16.2 created 1972, modified 2003]

EC 1.14.16.3

Accepted name: anthranilate 3-monooxygenase

Reaction: anthranilate + tetrahydrobiopterin + O2 = 3-hydroxyanthranilate + dihydrobiopterin + H2O

Other name(s): anthranilate 3-hydroxylase; anthranilate hydroxylase; anthranilic hydroxylase; anthranilic acid hydroxylase

Systematic name: anthranilate,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe2+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-79-4

References:

1. Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071-1081. [PMID: 5789774]

2. Nair, P.M. and Vaidyanathan, C.S. Anthranilic acid hydroxylase from Tecoma stans. Biochim. Biophys. Acta 110 (1965) 521-531.

[EC 1.14.16.3 created 1972]

EC 1.14.16.4

Accepted name: tryptophan 5-monooxygenase

Reaction: L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin

For diagram click here.

Other name(s): L-tryptophan hydroxylase; indoleacetic acid-5-hydroxylase; tryptophan 5-hydroxylase; tryptophan hydroxylase

Systematic name: L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9037-21-2

References:

1. Friedman, P.A., Kappelman, A.H. and Kaufman, S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247 (1972) 4165-4173. [PMID: 4402511]

2. Hamon, M., Bourgoin, S., Artaud, F. and Glowinski, J. The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium. J. Neurochem. 33 (1979) 1031-1042. [PMID: 315449]

3. Ichiyama, A., Nakamura, S., Nishizuka, Y. and Hayaishi, O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 245 (1970) 1699-1709. [PMID: 5309585]

4. Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071-1081. [PMID: 5789774]

5. Wang, L., Erlandsen, H., Haavik, J., Knappskog, P.M. and Stevens, R.C. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry 41 (2002) 12569-12574. [PMID: 12379098]

[EC 1.14.16.4 created 1972, modified 2003]

EC 1.14.16.5

Accepted name: alkylglycerol monooxygenase

Reaction: 1-alkyl-sn-glycerol + tetrahydrobiopterin + O2 = 1-O-alkyl-sn-glycerol + dihydrobiopterin + H2O

Other name(s): glyceryl-ether monooxygenase; glyceryl-ether cleaving enzyme; alkylglycerol monooxygenase; glyceryl ether oxygenase; glyceryl etherase; O-alkylglycerol monooxygenase

Systematic name: 1-alkyl-sn-glycerol,tetrahydrobiopterin:oxygen oxidoreductase

Comments: The enzyme cleaves alkylglycerols, but does not cleave alkenylglycerols (plasmalogens). Requires reduced glutathione and phospholipids for full activity. The product spontaneously breaks down to form a fatty aldehyde and glycerol.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-82-9

References:

1. Ishibashi, T. and Imai, Y. Solubilization and partial characterization of alkylglycerol monooxygenase from rat liver microsomes. Eur. J. Biochem. 132 (1983) 23-27. [PMID: 6840084]

2. Pfleger, E.C., Piantadosi, C. and Snyder, F. The biocleavage of isomeric glyceryl ethers by soluble liver enzymes in a variety of species. Biochim. Biophys. Acta 144 (1967) 633-648. [PMID: 4383918]

3. Snyder, F., Malone, B. and Piantadosi, C. Tetrahydropteridine-dependent cleavage enzyme for O-alkyl lipids: substrate specificity. Biochim. Biophys. Acta 316 (1973) 259-265. [PMID: 4355017]

4. Soodsma, J.F., Piantadosi, C. and Snyder, F. Partial characterization of the alkylglycerol cleavage enzyme system of rat liver. J. Biol. Chem. 247 (1972) 3923-3929. [PMID: 4402391]

5. Tietz, A., Lindberg, M. and Kennedy, E.P. A new pteridine-requiring enzyme system for the oxidation of glyceryl ethers. J. Biol. Chem. 239 (1964) 4081-4090. [PMID: 14247652]

6. Taguchi, H. and Armarego, W.L. Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism. Med. Res. Rev. 18 (1998) 43-89. [PMID: 9436181]

[EC 1.14.16.5 created 1972 as EC 1.14.99.17, transferred 1976 to EC 1.14.16.5, modified 2010]

EC 1.14.16.6

Accepted name: mandelate 4-monooxygenase

Reaction: (S)-2-hydroxy-2-phenylacetate + tetrahydrobiopterin + O2 = (S)-4-hydroxymandelate + dihydrobiopterin + H2O

Glossary: (S)-4-hydroxymandelate = (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate

Other name(s): L-mandelate 4-hydroxylase; mandelic acid 4-hydroxylase

Systematic name: (S)-2-hydroxy-2-phenylacetate,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)

Comments: Requires Fe2+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 39459-82-0

References:

1. Bhat, S.G. and Vaidyanathan, C.S. Purifications and properties of L-mandelate-4-hydroxylase from Pseudomonas convexa. Arch. Biochem. Biophys. 176 (1976) 314-323. [PMID: 9909]

[EC 1.14.16.6 created 1984]

EC 1.14.16.7

Accepted name: phenylalanine 3-monooxygenase

Reaction: L-phenylalanine + tetrahydrobiopterin + O2 = 3-hydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin

Glossary: 3-hydroxy-L-phenylalanine = meta-L-tyrosine = 3-(3-hydroxyphenyl)-L-alanine

Other name(s): PacX; phenylalanine 3-hydroxylase

Systematic name: L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: The enzyme from the bacterium Streptomyces coeruleorubidus forms 3-hydroxy-L-phenylalanine (i.e. m-L-tyrosine), which is one of the building blocks in the biosynthesis of the uridyl peptide antibiotics pacidamycins.

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

References:

1. Zhang, W., Ames, B.D. and Walsh, C.T. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis. Biochemistry 50 (2011) 5401-5403. [PMID: 21615132]

[EC 1.14.16.7 created 2014]


EC 1.14.17 With ascorbate as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.17.1 dopamine β-monooxygenase
EC 1.14.17.2 deleted, included in EC 1.14.18.1
EC 1.14.17.3 peptidylglycine monooxygenase
EC 1.14.17.4 aminocyclopropanecarboxylate oxidase


EC 1.14.17.1

Accepted name: dopamine β-monooxygenase

Reaction: dopamine + ascorbate + O2 = noradrenaline + dehydroascorbate + H2O

For diagram click here.

Glossary: dopamine = 4-(2-aminoethyl)benzene-1,2-diol

Other name(s): dopamine β-hydroxylase; MDBH (membrane-associated dopamine β-monooxygenase); SDBH (soluble dopamine β-monooxygenase); dopamine-B-hydroxylase; oxygenase, dopamine β-mono-; 3,4-dihydroxyphenethylamine β-oxidase; 4-(2-aminoethyl)pyrocatechol β-oxidase; dopa β-hydroxylase; dopamine β-oxidase; dopamine hydroxylase; phenylamine β-hydroxylase; (3,4-dihydroxyphenethylamine)β-mono-oxygenase; DβM

Systematic name: 3,4-dihydroxyphenethylamine,ascorbate:oxygen oxidoreductase (β-hydroxylating)

Comments: A copper protein. Stimulated by fumarate. Formerly EC 1.14.2.1.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9013-38-1

References:

1. Friedman, S. and Kaufman, S. 3,4-Dihydroxyphenylethylamine β-hydroxylase. Physical properties, copper content, and role of copper in the catalytic activity. J. Biol. Chem. 240 (1965) 4763-4773. [PMID: 5846992]

2. Levin, E.Y., Levenberg, B. and Kaufman, S. The enzymatic conversion of 3,4-dihydroxyphenylethylamine to norepinephrine. J. Biol. Chem. 235 (1960) 2080-2086.

[EC 1.14.17.1 created 1965 as EC 1.14.2.1, transferred 1972 to EC 1.14.17.1]

[EC 1.14.17.2 Deleted entry: 4-coumarate 3-monooxygenase. Now included with EC 1.14.18.1 monophenol monooxygenase (EC 1.14.17.2 created 1972, deleted 1984)]

EC 1.14.17.3

Accepted name: peptidylglycine monooxygenase

Reaction: peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O

Other name(s): peptidylglycine 2-hydroxylase; peptidyl α-amidating enzyme; peptide-α-amide synthetase; synthase, peptide α-amide; peptide α-amidating enzyme; peptide α-amide synthase; peptidylglycine α-hydroxylase; peptidylglycine α-amidating monooxygenase; PAM-A; PAM-B; PAM

Systematic name: peptidylglycine,ascorbate:oxygen oxidoreductase (2-hydroxylating)

Comments: A copper protein. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalysed by EC 4.3.2.5 peptidylamidoglycolate lyase. Involved in the final step of biosynthesis of α-melanotropin and related biologically active peptides.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 90597-47-0

References:

1. Bradbury, A.F., Finnie, M.D.A. and Smyth, D.G. Mechanism of C-terminal amide formation by pituitary enzymes. Nature (Lond.) 298 (1982) 686-688. [PMID: 7099265]

2. Bradbury, A.F. and Smyth, D.G. Enzyme-catalysed peptide amidation. Isolation of a stable intermediate formed by reaction of the amidating enzyme with an imino acid. Eur. J. Biochem. 169 (1987) 579-584. [PMID: 3691506]

3. Glembotski, C.G.Further characterization of the peptidyl α-amidating enzyme in rat anterior pituitary secretory granules. Arch. Biochem. Biophys. 241 (1985) 673-683. [PMID: 2994573]

4. Katopodis, A.G., Ping, D. and May, S.W. A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of α-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine α-amidating monooxygenase in peptide amidation. Biochemistry 29 (1990) 6115-6120. [PMID: 2207061]

5.Murthy, A.S.N., Keutmann, H.T. and Eipper, B.A. Further characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. Mol. Endocrinol. 1 (1987) 290-299. [PMID: 3453894]

6.Murthy, A.S.N., Mains, R.E. and Eipper, B.A. Purification and characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. J.Biol. Chem. 261 (1986) 1815-1822. [PMID: 3944110]

[EC 1.14.17.3 created 1989]

EC 1.14.17.4

Accepted name: aminocyclopropanecarboxylate oxidase

Reaction: 1-aminocyclopropane-1-carboxylate + ascorbate + O2 = ethene + cyanide + dehydroascorbate + CO2 + 2 H2O

For diagram click here.

Glossary: ethene = ethylene

Other name(s): ACC oxidase; ethylene-forming enzyme

Systematic name: 1-aminocyclopropane-1-carboxylate oxygenase (ethene-forming)

Comments: A nonheme iron enzyme. Requires CO2 for activity. In the enzyme from plants, the ethene has signalling functions such as stimulation of fruit-ripening.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 98668-53-2

References:

1. Zhang, Z.H., Schofield, C.J., Baldwin, J.E., Thomas, P. and John, P. Expression, purification and characterization of 1-aminocyclopropane-1-carboxylate oxidase from tomato in Escherichia coli. Biochem. J. 307 (1995) 77-85. [PMID: 7717997]

2. Zhang, Z.H., Barlow, J.N., Baldwin, J.E. and Schofield, C.J. Metal-catalyzed oxidation and mutagenesis studies on the iron(II) binding site of 1-aminocyclopropane-1-carboxylate oxidase. Biochemistry 36 (1997) 15999-16007. [PMID: 9398335]

3. Pirrung, M.C. Ethylene biosynthesis from 1-aminocyclopropanecarboxylic acid. Acc. Chem. Res. 32 (1999) 711-718.

4. Charng, Y., Chou, S.J., Jiaang, W.T., Chen, S.T. and Yang, S.F. The catalytic mechanism of 1-aminocyclopropane-1-carboxylic acid oxidase. Arch. Biochem. Biophys. 385 (2001) 179-185. [PMID: 11361015]

5. Thrower, J.S., Blalock, R. and Klinman, J.P. Steady-state kinetics of substrate binding and iron release in tomato ACC oxidase. Biochemistry 40 (2001) 9717-9724. [PMID: 11583172]

[EC 1.14.17.4 created 2003]


EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.18.1 tyrosinase
EC 1.14.18.2 CMP-N-acetylneuraminate monooxygenase
EC 1.14.18.3 methane monooxygenase (particulate)
EC 1.14.18.4 phosphatidylcholine 12-monooxygenase
EC 1.14.18.5 sphingolipid C4-monooxygenase
EC 1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase
EC 1.14.18.7 dihydroceramide fatty acyl 2-hydroxylase
EC 1.14.18.8 7α-hydroxycholest-4-en-3-one 12α-hydroxylase
EC 1.14.18.9 methylsterol monooxygenase

EC 1.14.18.1

Accepted name: tyrosinase

Reaction: (1) L-tyrosine + O2 = dopaquinone + H2O (overall reaction)
(1a) L-tyrosine + ½ O2 = L-dopa
(1b) L-dopa + ½ O2 = dopaquinone + H2O
(2) 2 L-dopa + O2 = 2 dopaquinone + 2 H2O

For diagram of reaction click here.

Other name(s): monophenol monooxygenase; phenolase; monophenol oxidase; cresolase; monophenolase; tyrosine-dopa oxidase; monophenol monooxidase; monophenol dihydroxyphenylalanine:oxygen oxidoreductase; N-acetyl-6-hydroxytryptophan oxidase; monophenol, dihydroxy-L-phenylalanine oxygen oxidoreductase; o-diphenol:O2 oxidoreductase; phenol oxidase

Systematic name: L-tyrosine,L-dopa:oxygen oxidoreductase

Comments: A type III copper protein found in a broad variety of bacteria, fungi, plants, insects, crustaceans, and mammals, which is involved in the synthesis of betalains and melanin. The enzyme, which is activated upon binding molecular oxygen, can catalyse both a monophenolase reaction cycle (reaction 1) or a diphenolase reaction cycle (reaction 2). During the monophenolase cycle, one of the bound oxygen atoms is transferred to a monophenol (such as L-tyrosine), generating an o-diphoenol intermediate, which is subsequently oxidized to an o-quinone and released, along with a water molecule. The enzyme remains in an inactive deoxy state, and is restored to the active oxy state by the binding of a new oxygen molecule. During the diphenolase cycle the enzyme binds an external diphenol molecule (such as L-dopa) and oxidizes it to an o-quinone that is released along with a water molecule, leaving the enzyme in the intermediate met state. The enzyme then binds a second diphenol molecule and repeats the process, ending in a deoxy state [7]. The second reaction is identical to that catalysed by the related enzyme catechol oxidase (EC 1.10.3.1). However, the latter can not catalyse the hydroxylation or monooxygenation of monophenols.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9002-10-2

References:

1. Dawson, C.R. and Tarpley, W.B. The copper oxidases. In: Sumner, J.B. and Myrbäck, K. (Eds), The Enzymes, 1st edn, vol. 2, Academic Press, New York, 1951, pp. 454-498.

2. Patil, S.S. and Zucker, M. Potato phenolases. Purification and properties. J. Biol. Chem. 240 (1965) 3938-3943. [PMID: 5842066]

3. Pomerantz, S.H. Separation, purification, and properties of two tyrosinases from hamster melanoma. J. Biol. Chem. 238 (1963) 2351-2357. [PMID: 13972077]

4. Robb, D.A. `Tyrosinase. In: Lontie, R. (Ed.), Copper Proteins and Copper Enzymes, vol. 2, CRC Press, Boca Raton, FL, 1984, pp. 207-240.

5. Sanchez-Ferrer, A., Rodriguez-Lopez, J.N., Garcia-Canovas, F. and Garcia-Carmona, F. Tyrosinase: a comprehensive review of its mechanism. Biochim. Biophys. Acta 1247 (1995) 1-11. [PMID: 7873577]

6. Steiner, U., Schliemann, W. and Strack, D. Assay for tyrosine hydroxylation activity of tyrosinase from betalain-forming plants and cell cultures. Anal. Biochem. 238 (1996) 72-75. [PMID: 8660589]

7. Rolff, M., Schottenheim, J., Decker, H. and Tuczek, F. Copper-O2 reactivity of tyrosinase models towards external monophenolic substrates: molecular mechanism and comparison with the enzyme. Chem Soc Rev 40 (2011) 4077-4098. [PMID: 21416076]

[EC 1.14.18.1 created 1972, modified 1976, modified 1980 (EC 1.14.17.2 created 1972, incorporated 1984), modified 2012]

EC 1.14.18.2

Accepted name: CMP-N-acetylneuraminate monooxygenase

Reaction: CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O2 + 2 H+ = CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H2O

Other name(s): CMP-N-acetylneuraminic acid hydroxylase; CMP-Neu5Ac hydroxylase; cytidine monophosphoacetylneuraminate monooxygenase; N-acetylneuraminic monooxygenase; cytidine-5'-monophosphate-N-acetylneuraminic acid hydroxylase

Systematic name: CMP-N-acetylneuraminate,ferrocytochrome-b5:oxygen oxidoreductase (N-acetyl-hydroxylating)

Comments: This enzyme contains both a Rieske-type [2Fe-2S] cluster and a second iron site. The ferricytochrome b5 produced is reduced by NADH and cytochrome-b5 reductase (EC 1.6.2.2). The enzyme can be activated by Fe2+ or Fe3+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 116036-67-0

References:

1. Shaw, L. and Schauer, R. The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol. Chem. Hoppe-Seyler 369 (1988) 477-486. [PMID: 3202954]

2. Kozutsumi, Y., Kawano, T., Yamakawa, T. and Suzuki, A. Participation of cytochrome b5 in CMP-N-acetylneuraminic acid hydroxylation in mouse liver cytosol. J. Biochem. (Tokyo) 109 (1990) 704-706.[PMID: 1964451]

3. Schneckenburger, P., Shaw, L. and Schauer, R. Purification, characterization and reconstitution of CMP-N-acetylneuraminate hydroxylase from mouse liver. Glycoconj. J. 11 (1994) 194-203. [PMID: 7841794]

4. Kawano, T., Koyama, S., Takematsu, H., Kozutsumi, Y., Kawasaki, H., Kawashima, S., Kawasaki, T. and Suzuki, A. Molecular cloning of cytidine monophospho-N-acetylneuraminic acid hydroxylase. Regulation of species- and tissue-specific expression of N-glycolylneuraminic acid. J. Biol. Chem. 270 (1995) 16458-16463. [PMID: 7608218]

5. Schlenzka, W., Shaw, L., Kelm, S., Schmidt, C.L., Bill, E., Trautwein, A.X., Lottspeich, F. and Schauer, R. CMP-N-acetylneuraminic acid hydroxylase: the first cytosolic Rieske iron-sulphur protein to be described in Eukarya. FEBS Lett. 385 (1996) 197-200. [PMID: 8647250]

[EC 1.14.18.2 created 1992 as EC 1.14.13.45, transferred 2003 to EC 1.14.18.2]

EC 1.14.18.3

Accepted name: methane monooxygenase (particulate)

Reaction: methane + quinol + O2 = methanol + quinone + H2O

Systematic name: methane,quinol:oxygen oxidoreductase

Comments: Contains copper. It is membrane-bound, in contrast to the soluble methane monooxygenase (EC 1.14.13.25).

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

References:

1. Shiemke, A.K., Cook, S.A., Miley, T. and Singleton, P. Detergent solubilization of membrane-bound methane monooxygenase requires plastoquinol analogs as electron donors. Arch. Biochem. Biophys. 321 (1995) 421-428. [PMID: 7646068]

2. Basu, P., Katterle, B., Andersson, K.K. and Dalton, H. The membrane-associated form of methane mono-oxygenase from Methylococcus capsulatus (Bath) is a copper/iron protein. Biochem. J. 369 (2003) 417-427. [PMID: 12379148]

3. Kitmitto, A., Myronova, N., Basu, P. and Dalton, H. Characterization and structural analysis of an active particulate methane monooxygenase trimer from Methylococcus capsulatus (Bath). Biochemistry 44 (2005) 10954-10965. [PMID: 16101279]

4. Balasubramanian, R. and Rosenzweig, A.C. Structural and mechanistic insights into methane oxidation by particulate methane monooxygenase. Acc. Chem. Res. 40 (2007) 573-580. [PMID: 17444606]

[EC 1.14.18.3 created 2011]

EC 1.14.18.4

Accepted name: phosphatidylcholine 12-monooxygenase

Reaction: a 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine + 2 ferrocytochrome b5 + O2 + 2 H+ = a 1-acyl-2-[(12R)-12-hydroxyoleoyl]-sn-glycero-3-phosphocholine + 2 ferricytochrome b5 + H2O

Glossary: ricinoleic acid = (9Z,12R)-12-hydroxyoctadec-9-enoic acid

Other name(s): ricinoleic acid synthase; oleate Δ12-hydroxylase; oleate Δ12-monooxygenase

Systematic name: 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine,ferrocytochrome-b5:oxygen oxidoreductase (12-hydroxylating)

Comments: The enzyme, characterized from the plant Ricinus communis (castor bean), is involved in production of the 12-hydroxylated fatty acid ricinoleate. The enzyme, which shares sequence similarity with fatty-acyl desaturases, requires a cytochrome b5 as the electron donor.

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

References:

1. Galliard, T. and Stumpf, P.K. Fat metabolism in higher plants. 30. Enzymatic synthesis of ricinoleic acid by a microsomal preparation from developing Ricinus communis seeds. J. Biol. Chem. 241 (1966) 5806-5812. [PMID: 4289003]

2. Moreau, R.A. and Stumpf, P.K. Recent studies of the enzymic-synthesis of ricinoleic acid by developing castor beans. Plant Physiol. 67 (1981) 672-676. [PMID: 16661734]

3. Smith, M.A., Jonsson, L., Stymne, S. and Stobart, K. Evidence for cytochrome b5 as an electron donor in ricinoleic acid biosynthesis in microsomal preparations from developing castor bean (Ricinus communis L.). Biochem. J. 287 (1992) 141-144. [PMID: 1417766]

4. Lin, J.T., McKeon, T.A., Goodrich-Tanrikulu, M. and Stafford, A.E. Characterization of oleoyl-12-hydroxylase in castor microsomes using the putative substrate, 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine. Lipids 31 (1996) 571-577. [PMID: 8784737]

5. Broun, P. and Somerville, C. Accumulation of ricinoleic, lesquerolic, and densipolic acids in seeds of transgenic Arabidopsis plants that express a fatty acyl hydroxylase cDNA from castor bean. Plant Physiol. 113 (1997) 933-942. [PMID: 9085577]

[EC 1.14.18.4 created 1984 as EC 1.14.13.26, transferred 2015 to EC 1.14.18.4]

EC 1.14.18.5

Accepted name: sphingolipid C4-monooxygenase

Reaction: a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4R)-4-hydroxysphinganine ceramide + 2 ferricytochrome b5 + H2O

Other name(s): sphinganine C4-monooxygenase; sphingolipid C4-hydroxylase; SUR2 (gene name); SBH1 (gene name); SBH2 (gene name); DEGS2 (gene name)

Systematic name: dihydroceramide,ferrocytochrome b5:oxygen oxidoreductase (C4-hydroxylating)

Comments: The enzyme, which belongs to the familiy of endoplasmic reticular cytochrome b5-dependent enzymes, is involved in the biosynthesis of sphingolipids in eukaryotes. Some enzymes are bifunctional and also catalyse EC 1.14.19.17, sphingolipid 4-desaturase [4].

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

References:

1. Haak, D., Gable, K., Beeler, T. and Dunn, T. Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p. J. Biol. Chem. 272 (1997) 29704-29710. [PMID: 9368039]

2. Grilley, M.M., Stock, S.D., Dickson, R.C., Lester, R.L. and Takemoto, J.Y. Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae. J. Biol. Chem. 273 (1998) 11062-11068. [PMID: 9556590]

3. Sperling, P., Ternes, P., Moll, H., Franke, S., Zähringer, U. and Heinz, E. Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana. FEBS Lett. 494 (2001) 90-94. [PMID: 11297741]

4. Ternes, P., Franke, S., Zähringer, U., Sperling, P. and Heinz, E. Identification and characterization of a sphingolipid Δ4-desaturase family. J. Biol. Chem. 277 (2002) 25512-25518. [PMID: 11937514]

5. Mizutani, Y., Kihara, A. and Igarashi, Y. Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation. FEBS Lett. 563 (2004) 93-97. [PMID: 15063729]

[EC 1.14.18.5 created 2012 as EC 1.14.13.169, transferred 2015 to EC 1.14.18.5]

EC 1.14.18.6

Accepted name: 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase

Reaction: a phytoceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (2'R)-2'-hydroxyphytoceramide + 2 ferricytochrome b5 + H2O

Glossary: a phytoceramide = a (4R)-4-hydroxysphinganine ceramide = an N-acyl-4-hydroxysphinganine

Other name(s): FA2H (gene name); SCS7 (gene name)

Systematic name: (4R)-4-hydroxysphinganine ceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)

Comments: The enzyme, characterized from yeast and mammals, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to (4R)-4-hydroxysphinganine during de novo ceramide synthesis. The enzymes from yeast and from mammals contain an N-terminal cytochrome b5 domain that acts as the direct electron donor to the desaturase active site. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.7, dihydroceramide fatty acyl 2-hydroxylase.

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

References:

1. Mitchell, A.G. and Martin, C.E. Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion protein, and its Arabidopsis thaliana homolog that lacks the cytochrome b5 domain both function in the α-hydroxylation of sphingolipid-associated very long chain fatty acids. J. Biol. Chem. 272 (1997) 28281-28288. [PMID: 9353282]

2. Dunn, T.M., Haak, D., Monaghan, E. and Beeler, T.J. Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a hydroxylase/desaturase domain. Yeast 14 (1998) 311-321. [PMID: 9559540]

3. Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J. and Hama, H. The human FA2H gene encodes a fatty acid 2-hydroxylase. J. Biol. Chem. 279 (2004) 48562-48568. [PMID: 15337768]

4. Eckhardt, M., Yaghootfam, A., Fewou, S.N., Zoller, I. and Gieselmann, V. A mammalian fatty acid hydroxylase responsible for the formation of α-hydroxylated galactosylceramide in myelin. Biochem. J. 388 (2005) 245-254. [PMID: 15658937]

5. Guo, L., Zhang, X., Zhou, D., Okunade, A.L. and Su, X. Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers. J. Lipid Res. 53 (2012) 1327-1335. [PMID: 22517924]

[EC 1.14.18.6 created 2015]

EC 1.14.18.7

Accepted name: dihydroceramide fatty acyl 2-hydroxylase

Reaction: a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (2'R)-2'-hydroxydihydroceramide + 2 ferricytochrome b5 + H2O

Glossary: a dihydroceramide = an N-acylsphinganine

Other name(s): FAH1 (gene name); FAH2 (gene name); plant sphingolipid fatty acid 2-hydroxylase

Systematic name: dihydroceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)

Comments: The enzyme, characterized from plants, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to sphinganine during de novo ceramide synthesis. The enzyme requires an external cytochrome b5 as the electron donor. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.6, 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase.

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

References:

1. Nagano, M., Ihara-Ohori, Y., Imai, H., Inada, N., Fujimoto, M., Tsutsumi, N., Uchimiya, H. and Kawai-Yamada, M. Functional association of cell death suppressor, Arabidopsis Bax inhibitor-1, with fatty acid 2-hydroxylation through cytochrome b5. Plant J. 58 (2009) 122-134. [PMID: 19054355]

2. Nagano, M., Takahara, K., Fujimoto, M., Tsutsumi, N., Uchimiya, H. and Kawai-Yamada, M. Arabidopsis sphingolipid fatty acid 2-hydroxylases (AtFAH1 and AtFAH2) are functionally differentiated in fatty acid 2-hydroxylation and stress responses. Plant Physiol. 159 (2012) 1138-1148. [PMID: 22635113]

3. Nagano, M., Uchimiya, H. and Kawai-Yamada, M. Plant sphingolipid fatty acid 2-hydroxylases have unique characters unlike their animal and fungus counterparts. Plant Signal Behav 7 (2012) 1388-1392. [PMID: 22918503]

[EC 1.14.18.7 created 2015]

EC 1.14.18.8

Accepted name: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase

Reaction: 7α-hydroxycholest-4-en-3-one + 2 ferrocytochrome b5 + 2 H+ + O2 = 7α,12α-dihydroxycholest-4-en-3-one + 2 ferricytochrome b5 + + H2O

For diagram of reaction click here.

Other name(s): 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; CYP12; sterol 12α-hydroxylase (ambiguous); HCO 12α-hydroxylase

Systematic name: 7α-hydroxycholest-4-en-3-one,ferrocytochrome-b5:oxygen oxidoreductase (12α-hydroxylating)

Comments: A P-450 heme-thiolate protein. Requires EC 1.6.2.4, NADPH—hemoprotein reductase and cytochrome b5 for maximal activity. This enzyme is important in bile acid biosynthesis, being responsible for the balance between the formation of cholic acid and chenodeoxycholic acid [2].

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

References:

1. Ishida, H., Noshiro, M., Okuda, K. and Coon, M.J. Purification and characterization of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase. J. Biol. Chem. 267 (1992) 21319-21323. [PMID: 1400444]

2. Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.I. and Björkhem, I. Molecular cloning and expression of rabbit sterol 12α-hydroxylase. J. Biol. Chem. 271 (1996) 32269-32275. [PMID: 8943286]

3. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8]

EC 1.14.18.9

Accepted name: methylsterol monooxygenase

Reaction: 4,4-dimethyl-5α-cholest-7-en-3β-ol + 6 ferrocytochrome b5 + 3 O2 + 6 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 6 ferricytochrome b5 + 4 H2O (overall reaction)
(1a) 4,4-dimethyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 4β-hydroxymethyl-4α-methyl-5α-cholest-7-en-3β-ol + 2 ferricytochrome b5 + H2O
(1b) 4β-hydroxymethyl-4α-methyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferricytochrome b5 + 2 H2O
(1c) 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 2 ferricytochrome b5 + H2O

For diagram of reaction click here

Other name(s): methylsterol hydroxylase; 4-methylsterol oxidase; 4,4-dimethyl-5α-cholest-7-en-3β-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating)

Systematic name: 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (hydroxylating)

Comments: Also acts on 4α-methyl-5α-cholest-7-en-3β-ol. The sterol can be based on cycloartenol as well as lanosterol.

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

References:

1. Miller, W.L., Kalafer, M.E., Gaylor, J.L. and Delwicke, C.V. Investigation of the component reactions of oxidative sterol demethylation. Study of the aerobic and anaerobic processes. Biochemistry 6 (1967) 2673-2678. [PMID: 4383278]

2. Gaylor, J.L. and Mason, H.S. Investigation of the component reactions of oxidative sterol demethylation. Evidence against participation of cytochrome P-450. J. Biol. Chem. 243 (1968) 4966-4972. [PMID: 4234469]

3. Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624-10629. [PMID: 7430141]

4. Fukushima, H., Grinstead, G.F. and Gaylor, J.L. Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-dependence of 4-methyl sterol oxidase. J. Biol. Chem. 256 (1981) 4822-4826. [PMID: 7228857]

5. Kawata, S., Trzaskos, J.M. and Gaylor, J.L. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J. Biol. Chem. 261 (1986) 3790-3799. [PMID: 3949790]

6. Pascal, S., Taton, M. and Rahier, A. Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation. J. Biol. Chem. 268 (1993) 11639-11654. [PMID: 8505296]

7. Rahier, A., Smith, M. and Taton, M. The role of cytochrome b5 in 4α-methyl-oxidation and C5(6) desaturation of plant sterol precursors. Biochem. Biophys. Res. Commun. 236 (1997) 434-437. [PMID: 9240456]

[EC 1.14.18.9 created 1972 as EC 1.14.99.16, transferred 2002 to EC 1.14.13.72, transferred 2017 to EC 1.14.18.9]


Continued with EC 1.14.19
Return to EC 1 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page