ExplorEnz: EC 1.14.14.1*

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1.14.14.139

Accepted name:

5β-cholestane-3α,7α-diol 12α-hydroxylase

Reaction:

(1) 5β-cholestane-3α,7α-diol + [reduced NADPH—hemoprotein reductase] + O₂ = 5β-cholestane-3α,7α,12α-triol + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 7α-hydroxycholest-4-en-3-one + [reduced NADPH—hemoprotein reductase] + O₂ = 7α,12α-dihydroxycholest-4-en-3-one + [oxidized NADPH—hemoprotein reductase] + H₂O
(3) chenodeoxycholate + [reduced NADPH—hemoprotein reductase] + O₂ = cholate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholesterol catabolism (rings A, B and C), click here

Glossary:

chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
cholate = 3α,7α-12α-trihydroxy-5β-cholan-24-oate

Other name(s):

5β-cholestane-3α,7α-diol 12α-monooxygenase; sterol 12α-hydroxylase (ambiguous); CYP8B1; cytochrome P450 8B1; 7α-hydroxycholest-4-en-3-one 12α-hydroxylase; 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; chenodeoxycholate 12α monooxygenase

Systematic name:

5β-cholestane-3α,7α-diol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in mammals. This is the key enzyme in the biosynthesis of the bile acid cholate. The enzyme can also hydroxylate 5β-cholestane-3α,7α-diol at the 25 and 26 position, but to a lesser extent [2].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB

References:

1.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis and metabolism of bile acids. Catalytic properties of different forms of cytochrome P-450. J. Biol. Chem. 255 (1980) 1643–1649. [PMID: 6766451]
2.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis of bile acids. Cytochrome P-450 LM4 and 12α-hydroxylation of 5β-cholestane-3α,7α-diol. Eur. J. Biochem. 125 (1982) 423–429. [DOI] [PMID: 6811268]
3.	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]
4.	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. [DOI] [PMID: 8943286]
5.	Lundell, K. and Wikvall, K. Gene structure of pig sterol 12α-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6α-hydroxylase (CYP4A21). Biochim. Biophys. Acta 1634 (2003) 86–96. [DOI] [PMID: 14643796]
6.	del Castillo-Olivares, A. and Gil, G. α1-Fetoprotein transcription factor is required for the expression of sterol 12α -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription. J. Biol. Chem. 275 (2000) 17793–17799. [DOI] [PMID: 10747975]
7.	Yang, Y., Zhang, M., Eggertsen, G. and Chiang, J.Y. On the mechanism of bile acid inhibition of rat sterol 12α-hydroxylase gene (CYP8B1) transcription: roles of α-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha. Biochim. Biophys. Acta 1583 (2002) 63–73. [DOI] [PMID: 12069850]
8.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
9.	Fan, L., Joseph, J.F., Durairaj, P., Parr, M.K. and Bureik, M. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol. Chem. 400 (2019) 625–628. [DOI] [PMID: 30465713]

[EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139 (EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, incorporated 2020) , modified 2020]

1.14.14.140

Transferred entry:

licodione synthase. Now included with EC 1.14.14.162, flavanone 2-hydroxylase

[EC 1.14.14.140 created 2004 as EC 1.14.13.87, transferred 2018 to EC 1.14.14.140, transferred 2018 to EC 1.14.14.162, deleted 2018]

1.14.14.141

Accepted name:

psoralen synthase

Reaction:

(+)-marmesin + [reduced NADPH—hemoprotein reductase] + O₂ = psoralen + [oxidized NADPH—hemoprotein reductase] + acetone + 2 H₂O

For diagram of reaction, click here

Glossary:

(+)-marmesin = (S)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-7H-furo[3,2-g]chromen-7-one
psoralen = 7H-furo[3,2-g]chromen-7-one

Other name(s):

CYP71AJ1

Systematic name:

(+)-marmesin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

This microsomal cytochrome P-450 (heme-thiolate) enzyme is rather specific for (+)-marmesin, although it can also accept 5-hydroxymarmesin to a much lesser extent. Furanocoumarins protect plants from fungal invasion and herbivore attack. (+)-Columbianetin, the angular furanocoumarin analogue of the linear furanocoumarin (+)-marmesin, acts as a competitive inhibitor even though it is not a substrate.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Larbat, R., Kellner, S., Specker, S., Hehn, A., Gontier, E., Hans, J., Bourgaud, F. and Matern, U. Molecular cloning and functional characterization of psoralen synthase, the first committed monooxygenase of furanocoumarin biosynthesis. J. Biol. Chem. 282 (2007) 542–554. [DOI] [PMID: 17068340]

[EC 1.14.14.141 created 2007 as EC 1.14.13.102, transferred 2018 to EC 1.14.14.141]

1.14.14.142

Accepted name:

8-dimethylallylnaringenin 2′-hydroxylase

Reaction:

sophoraflavanone B + [reduced NADPH—hemoprotein reductase] + O₂ = leachianone G + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of sophoraflavanone G biosynthesis, click here

Glossary:

dimethylallyl = prenyl = 3-methylbut-2-en-1-yl
lavandulyl = 5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl
leachianone G = (–)-(2S)-2′-hydroxy-8-prenylnaringenin = (–)-(2S)-2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-chromen-4-one
naringenin = 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
sophoraflavanone B = (–)-(2S)-8-prenylnaringenin = (–)-(2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-chromen-4-one

Other name(s):

8-DMAN 2′-hydroxylase

Systematic name:

sophoraflavanone-B,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2′-hydroxylating)

Comments:

A membrane-bound cytochrome P-450 (heme-thiolate) protein that is associated with the endoplasmic reticulum [1,2]. This enzyme is specific for sophoraflavanone B as substrate. Along with EC 2.5.1.70 (naringenin 8-dimethylallyltransferase) and EC 2.5.1.71 (leachianone G 2′′-dimethylallyltransferase), this enzyme forms part of the sophoraflavanone G biosynthetic pathway.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Yamamoto, H., Yatou, A. and Inoue, K. 8-Dimethylallylnaringenin 2′-hydroxylase, the crucial cytochrome P₄₅₀ mono-oxygenase for lavandulylated flavanone formation in Sophora flavescens cultured cells. Phytochemistry 58 (2001) 671–676. [DOI] [PMID: 11672730]
2.	Zhao, P., Inoue, K., Kouno, I. and Yamamoto, H. Characterization of leachianone G 2′′-dimethylallyltransferase, a novel prenyl side-chain elongation enzyme for the formation of the lavandulyl group of sophoraflavanone G in Sophora flavescens Ait. cell suspension cultures. Plant Physiol. 133 (2003) 1306–1313. [DOI] [PMID: 14551337]

[EC 1.14.14.142 created 2007 asEC 1.14.13.103, transferred 2018 to EC 1.14.14.142]

1.14.14.143

Accepted name:

(+)-menthofuran synthase

Reaction:

(+)-pulegone + [reduced NADPH—hemoprotein reductase] + O₂ = (+)-menthofuran + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of (â€“)-carvone, perillyl aldehyde and pulegone biosynthesis, click here and for mechanism of reaction, click here

Other name(s):

menthofuran synthase; (+)-pulegone 9-hydroxylase; (+)-MFS; cytochrome P450 menthofuran synthase

Systematic name:

(+)-pulegone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (9-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The conversion of substrate into product involves the hydroxylation of the syn-methyl (C₉), intramolecular cyclization to the hemiketal and dehydration to the furan [1]. This is the second cytochrome P-450-mediated step of monoterpene metabolism in peppermint, with the other step being catalysed by EC 1.14.14.99, (S)-limonene 3-monooxygenase [1].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Bertea, C.M., Schalk, M., Karp, F., Maffei, M. and Croteau, R. Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P₄₅₀ monooxygenase: cloning, functional expression, and characterization of the responsible gene. Arch. Biochem. Biophys. 390 (2001) 279–286. [DOI] [PMID: 11396930]
2.	Mahmoud, S.S. and Croteau, R.B. Menthofuran regulates essential oil biosynthesis in peppermint by controlling a downstream monoterpene reductase. Proc. Natl. Acad. Sci. USA 100 (2003) 14481–14486. [DOI] [PMID: 14623962]

[EC 1.14.14.143 created 2008 as EC 1.14.13.104, transferred 2018 to EC 1.14.14.143]

1.14.14.144

Accepted name:

abieta-7,13-diene hydroxylase

Reaction:

abieta-7,13-diene + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18-ol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here

Glossary:

abieta-7,13-diene = (4aS,4bR,10aS)-7-isopropyl-1,1,4a-trimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene
abieta-7,13-dien-18-ol = ((1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthren-1-yl)methanol

Other name(s):

abietadiene hydroxylase (ambiguous)

Systematic name:

abieta-7,13-diene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Funk, C. and Croteau, R. Diterpenoid resin acid biosynthesis in conifers: characterization of two cytochrome P450-dependent monooxygenases and an aldehyde dehydrogenase involved in abietic acid biosynthesis. Arch. Biochem. Biophys. 308 (1994) 258–266. [DOI] [PMID: 8311462]
2.	Funk, C., Lewinsohn, E., Vogel, B.S., Steele, C.L. and Croteau, R. Regulation of oleoresinosis in grand fir (Abies grandis) (coordinate induction of monoterpene and diterpene cyclases and two cytochrome P450-dependent diterpenoid hydroxylases by stem wounding). Plant Physiol. 106 (1994) 999–1005. [PMID: 12232380]

[EC 1.14.14.144 created 2009 as EC 1.14.13.108, modified 2012, transferred 2018 to EC 1.14.14.144]

1.14.14.145

Accepted name:

abieta-7,13-dien-18-ol hydroxylase

Reaction:

abieta-7,13-dien-18-ol + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = abieta-7,13-dien-18-oate + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) abieta-7,13-dien-18-ol + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18,18-diol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) abieta-7,13-dien-18,18-diol = abieta-7,13-dien-18-al + H₂O (spontaneous)
(1c) abieta-7,13-dien-18-al + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18-oate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here

Glossary:

abieta-7,13-dien-18-ol = ((1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthren-1-yl)methanol
abieta-7,13-dien-18-al = (1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carbaldehyde

Other name(s):

CYP720B1; PtAO; abietadienol hydroxylase (ambiguous)

Systematic name:

abieta-7,13-dien-18-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. This enzyme catalyses a step in the pathway of abietic acid biosynthesis. The activity has been demonstrated in cell-free stem extracts of Abies grandis (grand fir) and Pinus contorta (lodgepole pine) [1], and the gene encoding the enzyme has been identified in Pinus taeda (loblolly pine) [3]. The recombinant enzyme catalyses the oxidation of multiple diterpene alcohol and aldehydes, including levopimaradienol, isopimara-7,15-dienol, isopimara-7,15-dienal, dehydroabietadienol and dehydroabietadienal. It is not able to oxidize abietadiene.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Funk, C. and Croteau, R. Diterpenoid resin acid biosynthesis in conifers: characterization of two cytochrome P450-dependent monooxygenases and an aldehyde dehydrogenase involved in abietic acid biosynthesis. Arch. Biochem. Biophys. 308 (1994) 258–266. [DOI] [PMID: 8311462]
2.	Funk, C., Lewinsohn, E., Vogel, B.S., Steele, C.L. and Croteau, R. Regulation of oleoresinosis in grand fir (Abies grandis) (coordinate induction of monoterpene and diterpene cyclases and two cytochrome P450-dependent diterpenoid hydroxylases by stem wounding). Plant Physiol. 106 (1994) 999–1005. [PMID: 12232380]
3.	Ro, D.K., Arimura, G., Lau, S.Y., Piers, E. and Bohlmann, J. Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase. Proc. Natl. Acad. Sci. USA 102 (2005) 8060–8065. [DOI] [PMID: 15911762]

[EC 1.14.14.145 created 2009 as EC 1.14.13.109, modified 2012, transferred 2018 to EC 1.14.14.145]

1.14.14.146

Accepted name:

geranylgeraniol 18-hydroxylase

Reaction:

geranylgeraniol + [reduced NADPH—hemoprotein reductase] + O₂ = 18-hydroxygeranylgeraniol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of acyclic diterpenoid biosynthesis, click here

Glossary:

plaunotol = 18-hydroxygeranylgeraniol

Other name(s):

GGOH-18-hydroxylase

Systematic name:

geranylgeraniol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the plant Croton sublyratus.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Tansakul, P. and De-Eknamkul, W. Geranylgeraniol-18-hydroxylase: the last enzyme in the plaunotol biosynthetic pathway in Croton sublyratus. Phytochemistry 47 (1998) 1241–1246.

[EC 1.14.14.146 created 2009 as EC 1.14.13.110, transferred 2018 to EC 1.14.14.146]

1.14.14.147

Accepted name:

22α-hydroxysteroid 23-monooxygenase

Reaction:

(1) 3-epi-6-deoxocathasterone + [reduced NADPH—hemoprotein reductase] + O₂ = 6-deoxotyphasterol + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) (22S,24R)-22-hydroxy-5α-ergostan-3-one + [reduced NADPH—hemoprotein reductase] + O₂ = 3-dehydro-6-deoxoteasterone + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

cytochrome P450 90C1; CYP90D1; CYP90C1; 3-epi-6-deoxocathasterone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-23-hydroxylating); 3-epi-6-deoxocathasterone 23-monooxygenase

Systematic name:

22α-hydroxysteroid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-23-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in brassinosteroid biosynthesis in plants. The enzyme has a relaxed substrate specificity, and C-23 hydroxylation can occur at different stages in the pathway. In Arabidopsis thaliana two isozymes, encoded by the CYP90C1 and CYP90D1 genes, have redundant activities.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Kim, G.T., Fujioka, S., Kozuka, T., Tax, F.E., Takatsuto, S., Yoshida, S. and Tsukaya, H. CYP90C1 and CYP90D1 are involved in different steps in the brassinosteroid biosynthesis pathway in Arabidopsis thaliana. Plant J. 41 (2005) 710–721. [DOI] [PMID: 15703058]
2.	Ohnishi, T., Szatmari, A.M., Watanabe, B., Fujita, S., Bancos, S., Koncz, C., Lafos, M., Shibata, K., Yokota, T., Sakata, K., Szekeres, M. and Mizutani, M. C-23 hydroxylation by Arabidopsis CYP90C1 and CYP90D1 reveals a novel shortcut in brassinosteroid biosynthesis. Plant Cell 18 (2006) 3275–3288. [DOI] [PMID: 17138693]

[EC 1.14.14.147 created 2010 as EC 1.14.13.112, transferred 2018 to EC 1.14.14.147, modified 2022]

1.14.14.148

Accepted name:

angelicin synthase

Reaction:

(+)-columbianetin + [reduced NADPH—hemoprotein reductase] + O₂ = angelicin + [oxidized NADPH—hemoprotein reductase] + acetone + 2 H₂O

For diagram of psoralen biosynthesis, click here

Other name(s):

CYP71AJ4 (gene name)

Systematic name:

(+)-columbianetin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

This cytochrome P-450 (heme-thiolate) enzyme from wild parsnip is involved in the formation of angular furanocoumarins. Attacks its substrate by syn-elimination of hydrogen from C-3′.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Larbat, R., Hehn, A., Hans, J., Schneider, S., Jugde, H., Schneider, B., Matern, U. and Bourgaud, F. Isolation and functional characterization of CYP71AJ4 encoding for the first P₄₅₀ monooxygenase of angular furanocoumarin biosynthesis. J. Biol. Chem. 284 (2009) 4776–4785. [DOI] [PMID: 19098286]

[EC 1.14.14.148 created 2010 as EC 1.14.13.115, transferred 2018 to EC 1.14.14.148]

1.14.14.149

Accepted name:

5-epiaristolochene 1,3-dihydroxylase

Reaction:

5-epiaristolochene + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = capsidiol + 2 [oxidized NADPH—hemoprotein reductase] + 2 H₂O

click here

Other name(s):

5-epi-aristolochene 1,3-dihydroxylase; EAH; CYP71D20

Systematic name:

5-epiaristolochene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (1- and 3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Kinetic studies suggest that 1β-hydroxyepiaristolochene is mainly formed first followed by hydroxylation at C-3. However the reverse order via 3α-hydroxyepiaristolochene does occur.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Ralston, L., Kwon, S.T., Schoenbeck, M., Ralston, J., Schenk, D.J., Coates, R.M. and Chappell, J. Cloning, heterologous expression, and functional characterization of 5-epi-aristolochene-1,3-dihydroxylase from tobacco (Nicotiana tabacum). Arch. Biochem. Biophys. 393 (2001) 222–235. [DOI] [PMID: 11556809]
2.	Takahashi, S., Zhao, Y., O'Maille, P.E., Greenhagen, B.T., Noel, J.P., Coates, R.M. and Chappell, J. Kinetic and molecular analysis of 5-epiaristolochene 1,3-dihydroxylase, a cytochrome P₄₅₀ enzyme catalyzing successive hydroxylations of sesquiterpenes. J. Biol. Chem. 280 (2005) 3686–3696. [DOI] [PMID: 15522862]

[EC 1.14.14.149 created 2011 as EC 1.14.13.119, transferred 2018 to EC 1.14.14.149]

1.14.14.150

Accepted name:

costunolide synthase

Reaction:

germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = (+)-costunolide + [oxidized NADPH—hemoprotein reductase] + 2 H₂O (overall reaction)
(1a) germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate = (+)-costunolide + H₂O (spontaneous)

click here

Other name(s):

CYP71BL2

Systematic name:

germacra-1(10),4,11(13)-trien-12-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from chicory plants. The enzyme hydroxylates carbon C-6 of germacra-1(10),4,11(13)-trien-12-oate to give 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate, which spontaneously cyclises to form the lactone ring.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

de Kraker, J.W., Franssen, M.C., Joerink, M., de Groot, A. and Bouwmeester, H.J. Biosynthesis of costunolide, dihydrocostunolide, and leucodin. Demonstration of cytochrome p₄₅₀-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory. Plant Physiol. 129 (2002) 257–268. [DOI] [PMID: 12011356]

[EC 1.14.14.150 created 2011 as EC 1.14.13.120, transferred 2018 to EC 1.14.14.150]

1.14.14.151

Accepted name:

premnaspirodiene oxygenase

Reaction:

(–)-vetispiradiene + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = solavetivone + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) (–)-vetispiradiene + [reduced NADPH—hemoprotein reductase] + O₂ = solavetivol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) solavetivol + [reduced NADPH—hemoprotein reductase] + O₂ = solavetivone + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of solavetivone biosynthesis, click here

Glossary:

(–)-premnaspirodiene = (–)-vetispiradiene

Other name(s):

HPO; Hyoscymus muticus premnaspirodiene oxygenase; CYP71D55

Systematic name:

(–)-vetispiradiene,[reduced NADPH—hemoprotein reductase]:oxygen 2α-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from the plant Hyoscymus muticus also hydroxylates valencene at C-2 to give the α-hydroxy compound, nootkatol, and this is converted into nootkatone. 5-Epiaristolochene and epieremophilene are hydroxylated at C-2 to give a 2β-hydroxy derivatives that are not oxidized further.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Takahashi, S., Yeo, Y.S., Zhao, Y., O'Maille, P.E., Greenhagen, B.T., Noel, J.P., Coates, R.M. and Chappell, J. Functional characterization of premnaspirodiene oxygenase, a cytochrome P₄₅₀ catalyzing regio- and stereo-specific hydroxylations of diverse sesquiterpene substrates. J. Biol. Chem. 282 (2007) 31744–31754. [DOI] [PMID: 17715131]

[EC 1.14.14.151 created 2011 as EC 1.14.13.121, transferred 2018 to EC 1.14.14.151]

1.14.14.152

Accepted name:

β-amyrin 11-oxidase

Reaction:

β-amyrin + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = 11-oxo-β-amyrin + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 11α-hydroxy-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 11α-hydroxy-β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 11-oxo-β-amyrin + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of glycyrrhenate biosynthesis, click here

Other name(s):

CYP88D6

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Glycyrrhiza uralensis (Chinese licorice) that participates in the glycyrrhizin biosynthesis pathway. The enzyme is also able to oxidize 30-hydroxy-β-amyrin to 11α,30-dihydroxy-β-amyrin but this is not thought to be part of glycyrrhizin biosynthesis.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Seki, H., Ohyama, K., Sawai, S., Mizutani, M., Ohnishi, T., Sudo, H., Akashi, T., Aoki, T., Saito, K. and Muranaka, T. Licorice β-amyrin 11-oxidase, a cytochrome P₄₅₀ with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc. Natl. Acad. Sci. USA 105 (2008) 14204–14209. [DOI] [PMID: 18779566]

[EC 1.14.14.152 created 2011 as EC 1.14.13.134, transferred 2018 to EC 1.14.14.152]

1.14.14.153

Accepted name:

indole-2-monooxygenase

Reaction:

indole + [reduced NADPH—hemoprotein reductase] + O₂ = indolin-2-one + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Other name(s):

BX2 (gene name); CYP71C4 (gene name)

Systematic name:

indole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme is involved in the biosynthesis of protective and allelophatic benzoxazinoids in some plants, most commonly from the family of Poaceae (grasses).

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. [DOI] [PMID: 9235894]
2.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]

[EC 1.14.14.153 created 2012 as EC 1.14.13.137, transferred 2018 to EC 1.14.14.153]

1.14.14.154

Accepted name:

sterol 14α-demethylase

Reaction:

a 14α-methylsteroid + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = a Δ¹⁴-steroid + formate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) a 14α-methylsteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 14α-hydroxymethylsteroid + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) a 14α-hydroxysteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 14α-formylsteroid + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) a 14α-formylsteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a Δ¹⁴-steroid + formate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of sterol ring B, C, D modification, click here

Glossary:

obtusifoliol = 4α,14α-dimethyl-5α-ergosta-8,24(28)-dien-3β-ol or 4α,14α-dimethyl-24-methylene-5α-cholesta-8-en-3β-ol

Other name(s):

obtusufoliol 14-demethylase; lanosterol 14-demethylase; lanosterol 14α-demethylase; sterol 14-demethylase; CYP51 (gene name); ERG11 (gene name)

Systematic name:

sterol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (14-methyl cleaving)

Comments:

This cytochrome P-450 (heme-thiolate) enzyme acts on a range of steroids with a 14α-methyl group, such as obtusifoliol and lanosterol. The enzyme catalyses a hydroxylation and a reduction of the 14α-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 60063-87-8

References:

1.	Alexander, K., Akhtar, M., Boar, R.B., McGhie, J.F. and Barton, D.H.R. The removal of the 32-carbon atom as formic acid in cholesterol biosynthesis. J. Chem. Soc. Chem. Commun. (1972) 383–385.
2.	Yoshida, Y. and Aoyama, Y. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. I. Purification and spectral properties. J. Biol. Chem. 259 (1984) 1655–1660. [PMID: 6363414]
3.	Aoyama, Y., Yoshida, Y. and Sato, R. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. II. Lanosterol metabolism by purified P-450¹⁴DM and by intact microsomes. J. Biol. Chem. 259 (1984) 1661–1666. [PMID: 6420412]
4.	Aoyama, Y. and Yoshida, Y. Different substrate specificities of lanosterol 14α-demethylase (P-450_14DM) of Saccharomyces cerevisiae and rat liver of 24-methylene-24,25-dihydrolanosterol and 24,25-dihydrolanosterol. Biochem. Biophys. Res. Commun. 178 (1991) 1064–1071. [DOI] [PMID: 1872829]
5.	Aoyama, Y. and Yoshida, Y. The 4β-methyl group of substrate does not affect the activity of lanosterol 14α-demethylase (P₄₅₀14DM) of yeast: differences between the substrate recognition by yeast and plant sterol 14α-demethylases. Biochem. Biophys. Res. Commun. 183 (1992) 1266–1272. [DOI] [PMID: 1567403]
6.	Bak, S., Kahn, R.A., Olsen, C.E. and Halkier, B.A. Cloning and expression in Escherichia coli of the obtusifoliol 14α-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P₄₅₀ orthologous to the sterol 14α-demethylases (CYP51) from fungi and mammals. Plant J. 11 (1997) 191–201. [DOI] [PMID: 9076987]

[EC 1.14.14.154 created 2001 as EC 1.14.13.70, modified 2013, transferred 2018 EC 1.14.14.154]

1.14.14.155

Accepted name:

3,6-diketocamphane 1,2-monooxygenase

Reaction:

(–)-bornane-2,5-dione + O₂ + FMNH₂ = (–)-5-oxo-1,2-campholide + FMN + H₂O

Glossary:

(–)-bornane-2,5-dione = 3,6-diketocamphane

Other name(s):

3,6-diketocamphane lactonizing enzyme; 3,6-DKCMO

Systematic name:

(–)-bornane-2,5-dione,FMNH₂:oxygen oxidoreductase (1,2-lactonizing)

Comments:

A Baeyer-Villiger monooxygenase isolated from camphor-grown strains of Pseudomonas putida and encoded on the cam plasmid. Involved in the degradation of (–)-camphor. Requires a dedicated NADH—FMN reductase [cf. EC 1.5.1.42, FMN reductase (NADH)] [1,2]. The product spontaneously converts to [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB

References:

Iwaki, H., Grosse, S., Bergeron, H., Leisch, H., Morley, K., Hasegawa, Y. and Lau, P.C. Camphor pathway redux: functional recombinant expression of 2,5- and 3,6-diketocamphane monooxygenases of Pseudomonas putida ATCC 17453 with their cognate flavin reductase catalyzing Baeyer-Villiger reactions. Appl. Environ. Microbiol. 79 (2013) 3282–3293. [PMID: 23524667]

Isupov, M.N., Schroder, E., Gibson, R.P., Beecher, J., Donadio, G., Saneei, V., Dcunha, S.A., McGhie, E.J., Sayer, C., Davenport, C.F., Lau, P.C., Hasegawa, Y., Iwaki, H., Kadow, M., Balke, K., Bornscheuer, U.T., Bourenkov, G. and Littlechild, J.A. The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Acta Crystallogr. D Biol. Crystallogr. 71 (2015) 2344–2353. [PMID: 26527149]

[EC 1.14.14.155 created 2018]

1.14.14.156

Accepted name:

tryptophan N-monooxygenase

Reaction:

L-tryptophan + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = (E)-indol-3-ylacetaldoxime + 2 [oxidized NADPH—hemoprotein reductase] + CO₂ + 3 H₂O (overall reaction)
(1a) L-tryptophan + [reduced NADPH—hemoprotein reductase] + O₂ = N-hydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) N-hydroxy-L-tryptophan + [reduced NADPH—hemoprotein reductase] + O₂ = N,N-dihydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H₂O
(1c) N,N-dihydroxy-L-tryptophan = (E)-indol-3-ylacetaldoxime + CO₂ + H₂O

Other name(s):

tryptophan N-hydroxylase; CYP79B1; CYP79B2; CYP79B3

Systematic name:

L-tryptophan,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Arabidopsis thaliana. This enzyme catalyses two successive N-hydroxylations of L-tryptophan, the first steps in the biosynthesis of both auxin and the indole alkaloid phytoalexin camalexin. The product of the two hydroxylations, N,N-dihydroxy-L-tryptophan, is extremely labile and dehydrates spontaneously. The dehydrated product is then subject to a decarboxylation that produces an oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Mikkelsen, M.D., Hansen, C.H., Wittstock, U. and Halkier, B.A. Cytochrome P₄₅₀ CYP79B2 from Arabidopsis catalyzes the conversion of tryptophan to indole-3-acetaldoxime, a precursor of indole glucosinolates and indole-3-acetic acid. J. Biol. Chem. 275 (2000) 33712–33717. [DOI] [PMID: 10922360]
2.	Hull, A.K., Vij, R. and Celenza, J.L. Arabidopsis cytochrome P₄₅₀s that catalyze the first step of tryptophan-dependent indole-3-acetic acid biosynthesis. Proc. Natl. Acad. Sci. USA 97 (2000) 2379–2384. [DOI] [PMID: 10681464]
3.	Zhao, Y., Hull, A.K., Gupta, N.R., Goss, K.A., Alonso, J., Ecker, J.R., Normanly, J., Chory, J. and Celenza, J.L. Trp-dependent auxin biosynthesis in Arabidopsis: involvement of cytochrome P₄₅₀s CYP79B2 and CYP79B3. Genes Dev. 16 (2002) 3100–3112. [DOI] [PMID: 12464638]
4.	Naur, P., Hansen, C.H., Bak, S., Hansen, B.G., Jensen, N.B., Nielsen, H.L. and Halkier, B.A. CYP79B1 from Sinapis alba converts tryptophan to indole-3-acetaldoxime. Arch. Biochem. Biophys. 409 (2003) 235–241. [DOI] [PMID: 12464264]

[EC 1.14.14.156 created 2011 as EC 1.14.13.125, transferred 2018 to EC 1.14.14.156]

1.14.14.157

Accepted name:

indolin-2-one monooxygenase

Reaction:

indolin-2-one + [reduced NADPH—hemoprotein reductase] + O₂ = 3-hydroxyindolin-2-one + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Other name(s):

BX3 (gene name); CYP71C2 (gene name)

Systematic name:

indolin-2-one,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. [DOI] [PMID: 9235894]
2.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]

[EC 1.14.14.157 created 2012 as EC 1.14.13.138, transferred 2018 to EC 1.14.14.157]

1.14.14.158

Accepted name:

carotenoid ε hydroxylase

Reaction:

(1) α-carotene + [reduced NADPH-hemoprotein reductase] + O₂ = α-cryptoxanthin + [oxidized NADPH-hemoprotein reductase] + H₂O
(2) zeinoxanthin + [reduced NADPH-hemoprotein reductase] + O₂ = lutein + [oxidized NADPH-hemoprotein reductase] + H₂O

For diagram of lutein biosynthesis, click here

Other name(s):

CYP97C1; LUT1; CYP97C; carotene ε-monooxygenase

Systematic name:

α-carotene,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB

References:

1.	Pogson, B., McDonald, K.A., Truong, M., Britton, G. and DellaPenna, D. Arabidopsis carotenoid mutants demonstrate that lutein is not essential for photosynthesis in higher plants. Plant Cell 8 (1996) 1627–1639. [DOI] [PMID: 8837513]
2.	Tian, L., Musetti, V., Kim, J., Magallanes-Lundback, M. and DellaPenna, D. The Arabidopsis LUT1 locus encodes a member of the cytochrome P₄₅₀ family that is required for carotenoid ε-ring hydroxylation activity. Proc. Natl. Acad. Sci. USA 101 (2004) 402–407. [DOI] [PMID: 14709673]
3.	Stigliani, A.L., Giorio, G. and D'Ambrosio, C. Characterization of P450 carotenoid β- and ε-hydroxylases of tomato and transcriptional regulation of xanthophyll biosynthesis in root, leaf, petal and fruit. Plant Cell Physiol. 52 (2011) 851–865. [PMID: 21450689]
4.	Chang, S., Berman, J., Sheng, Y., Wang, Y., Capell, T., Shi, L., Ni, X., Sandmann, G., Christou, P. and Zhu, C. Cloning and functional characterization of the maize (Zea mays L.) carotenoid ε hydroxylase gene. PLoS One 10:e0128758 (2015). [PMID: 26030746]
5.	Reddy, C.S., Lee, S.H., Yoon, J.S., Kim, J.K., Lee, S.W., Hur, M., Koo, S.C., Meilan, J., Lee, W.M., Jang, J.K., Hur, Y., Park, S.U. and Kim, A.YB. Molecular cloning and characterization of carotenoid pathway genes and carotenoid content in Ixeris dentata var. albiflora. Molecules 22 (2017) . [DOI] [PMID: 28858245]

[EC 1.14.14.158 created 2011 as EC 1.14.99.45, transferred 2018 to EC 1.14.14.158]

1.14.14.159

Accepted name:

dolabradiene monooxygenase

Reaction:

(1) dolabradiene + O₂ + [reduced NADPH—hemoprotein reductase] = 15,16-epoxydolabrene + H₂O + [oxidized NADPH—hemoprotein reductase]
(2) 15,16-epoxydolabrene + O₂ + [reduced NADPH—hemoprotein reductase] = 3β-hydroxy-15,16-epoxydolabrene + H₂O + [oxidized NADPH—hemoprotein reductase]

Glossary:

dolabradiene = (4aS,4bR,7S,8aR,10aS)-7-ethenyl-4b,7,10a-trimethyl-1-methylidenetetradecahydrophenanthrene

Other name(s):

CYP71Z16 (gene name)

Systematic name:

dolabradiene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3β-hydroxy-15,16-epoxydolabrene-forming)

Comments:

A cytochrome P-450 (heme thiolate) enzyme characterized from maize. The enzyme catalyses the epoxidation of dolabradiene at C-16, followed by hydroxylation at C-3.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

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

[EC 1.14.14.159 created 2018]

1.14.14.160

Accepted name:

zealexin A1 synthase

Reaction:

(S)-β-macrocarpene + 3 O₂ + 3 [reduced NADPH—hemoprotein reductase] = zealexin A1 + 4 H₂O + 3 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) (S)-β-macrocarpene + O₂ + [reduced NADPH—hemoprotein reductase] = [(4S)-4-(5,5-dimethylcyclohex-1-en-1-yl)-cyclohex-1-en-1-yl]methanol + H₂O + [oxidized NADPH—hemoprotein reductase]
(1b) [(4S)-4-(5,5-dimethylcyclohex-1-en-1-yl)-cyclohex-1-en-1-yl] methanol + O₂ + [reduced NADPH—hemoprotein reductase] = (4S)-4-(5,5-dimethylcyclohex-1-en-1-yl)cyclohex-1-ene-1-carbaldehyde + 2 H₂O + [oxidized NADPH—hemoprotein reductase]
(1c) (4S)-4-(5,5-dimethylcyclohex-1-en-1-yl)cyclohex-1-ene-1-carbaldehyde + O₂ + [reduced NADPH—hemoprotein reductase] = zealexin A1 + H₂O + [oxidized NADPH—hemoprotein reductase]

For diagram of zealexin biosynthesis, click here

Glossary:

(S)-β-macrocarpene = (1′S)-4′,5,5-trimethyl-1,1′-bi(cyclohexane)-1,3′-diene
zealexin A1 = (4S)-4-(5,5-dimethylcyclohex-1-en-1-yl)cyclohex-1-ene-1-carboxylate

Other name(s):

CYP71Z18 (gene name)

Systematic name:

(S)-β-macrocarpene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (zealexin A1-forming)

Comments:

A cytochrome P-450 (heme thiolate) enzyme characterized from maize. The enzyme sequentially oxidizes(S)-β-macrocarpene via alcohol and aldehyde intermediates to form zealexin A1, a maize phytoalexin that provides biochemical protection against fungal infection.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Mao, H., Liu, J., Ren, F., Peters, R.J. and Wang, Q. Characterization of CYP71Z18 indicates a role in maize zealexin biosynthesis. Phytochemistry 121 (2016) 4–10. [PMID: 26471326]

[EC 1.14.14.160 created 2018]

1.14.14.161

Accepted name:

nepetalactol monooxygenase

Reaction:

(+)-cis,trans-nepetalactol + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = 7-deoxyloganetate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) (+)-cis,trans-nepetalactol + [reduced NADPH—hemoprotein reductase] + O₂ = 7-deoxyloganetic alcohol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 7-deoxyloganetic alcohol + [reduced NADPH—hemoprotein reductase] + O₂ = iridotrial + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) iridotrial + [reduced NADPH—hemoprotein reductase] + O₂ = 7-deoxyloganetate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of gibberellin A₁₂ biosynthesis, click here

Glossary:

(+)-cis,trans-nepetalactol = (4aS,7S,7aR)-4,7-dimethyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-1-ol
7-deoxyloganetate = (1S,4aS,7S,7aR)-1-hydroxy-7-methyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate

Other name(s):

CYP76A26 (gene name); iridoid oxidase (misleading)

Systematic name:

(+)-cis,trans-nepetalactol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)

Comments:

The enzyme, characterized from the plant Catharanthus roseus, is a cytochrome P-450 (heme thiolate) protein. It catalyses three successive reactions in the pathway leading to biosynthesis of monoterpenoid indole alkaloids.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Miettinen, K., Dong, L., Navrot, N., Schneider, T., Burlat, V., Pollier, J., Woittiez, L., van der Krol, S., Lugan, R., Ilc, T., Verpoorte, R., Oksman-Caldentey, K.M., Martinoia, E., Bouwmeester, H., Goossens, A., Memelink, J. and Werck-Reichhart, D. The seco-iridoid pathway from Catharanthus roseus. Nat. Commun. 5:3606 (2014). [PMID: 24710322]

[EC 1.14.14.161 created 2018]

1.14.14.162

Accepted name:

flavanone 2-hydroxylase

Reaction:

a flavanone + [reduced NADPH—hemoprotein reductase] + O₂ = a 2-hydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of licodione biosynthesis, click here

Other name(s):

CYP93G2 (gene name); CYP93B1 (gene name); (2S)-flavanone 2-hydroxylase; licodione synthase

Systematic name:

flavanone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-hydroxylating)

Comments:

A cytochrome P-450 (heme thiolate) plant enzyme that catalyses the 2-hydroxylation of multiple flavanones such as (2S)-naringenin, (2S)-eriodictyol, (2S)-pinocembrin, and (2S)-liquiritigenin. The products are meta-stable and exist in an equilibrium with open forms such as 1-(4-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propane-1,3-dione.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Otani, K., Takahashi, T., Furuya, T. and Ayabe, S. Licodione synthase, a cytochrome P₄₅₀ monooxygenase catalyzing 2-hydroxylation of 5-deoxyflavanone, in cultured Glycyrrhiza echinata L. cells. Plant Physiol. 105 (1994) 1427–1432. [PMID: 12232298]
2.	Akashi, T., Aoki, T. and Ayabe, S. Identification of a cytochrome P₄₅₀ cDNA encoding (2S)-flavanone 2-hydroxylase of licorice (Glycyrrhiza echinata L.; Fabaceae) which represents licodione synthase and flavone synthase II. FEBS Lett. 431 (1998) 287–290. [DOI] [PMID: 9708921]
3.	Du, Y., Chu, H., Chu, I.K. and Lo, C. CYP93G2 is a flavanone 2-hydroxylase required for C-glycosylflavone biosynthesis in rice. Plant Physiol. 154 (2010) 324–333. [PMID: 20647377]

[EC 1.14.14.162 created 2018. EC 1.14.14.140 created 2004 as EC 1.14.13.87, transferred 2018 to EC 1.14.14.140, transferred 2018 to EC 1.14.14.162]

1.14.14.163

Accepted name:

(S)-1-hydroxy-N-methylcanadine 13-hydroxylase

Reaction:

(S)-1-hydroxy-cis-N-methylcanadine + [reduced NADPH—hemoprotein reductase] + O₂ = (13S,14R)-1,13-dihydroxy-cis-N-methylcanadine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of noscapine biosynthesis, click here

Other name(s):

CYP82X2 (gene name)

Systematic name:

(S)-1-hydroxy-cis-N-methylcanadine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (13-hydroxylating)

Comments:

The enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Dang, T.T., Chen, X. and Facchini, P.J. Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat. Chem. Biol. 11 (2015) 104–106. [DOI] [PMID: 25485687]
2.	Li, Y. and Smolke, C.D. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7:12137 (2016). [DOI] [PMID: 27378283]
3.	Li, Y., Li, S., Thodey, K., Trenchard, I., Cravens, A. and Smolke, C.D. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proc. Natl. Acad. Sci. USA 115 (2018) E3922–E3931. [DOI] [PMID: 29610307]

[EC 1.14.14.163 created 2018]

1.14.14.164

Accepted name:

fraxetin 5-hydroxylase

Reaction:

fraxetin + [reduced NADPH—hemoprotein reductase] + O₂ = sideretin (reduced form) + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

fraxetin = 7,8-dihydroxy-6-methoxy-2H-chromen-2-one
sideretin (reduced form) = 5,7,8-trihydroxy-6-methoxy-2H-chromen-2-one

Other name(s):

CYP82C4; fraxetin 5-monooxygenase

Systematic name:

fraxetin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (5-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in biosynthesis of iron(III)-chelating coumarins in higher plants.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Rajniak, J., Giehl, R.FH., Chang, E., Murgia, I., von Wiren, N. and Sattely, E.S. Biosynthesis of redox-active metabolites in response to iron deficiency in plants. Nat. Chem. Biol. 14 (2018) 442–450. [PMID: 29581584]

[EC 1.14.14.164 created 2018]

1.14.14.165

Accepted name:

indole-3-carbonyl nitrile 4-hydroxylase

Reaction:

indole-3-carbonyl nitrile + [reduced NADPH—hemoprotein reductase] + O₂ = 4-hydroxyindole-3-carbonyl nitrile + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

indole-3-carbonyl nitrile = 2-(1H-indole-3-yl)-2-oxoacetonitrile
4-hydroxyindole-3-carbonyl nitrile = 2-(4-hydroxy-1H-indole-3-yl)-2-oxoacetonitrile

Other name(s):

CYP82C2

Systematic name:

indole-3-carbonyl nitrile,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein characterized from the plant Arabidopsis thaliana. Involved in biosynthesis of small cyanogenic compounds that take part in pathogen defense. The enzyme also catalyses the 5-hydroxylation of xanthotoxin [1].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Kruse, T., Ho, K., Yoo, H.D., Johnson, T., Hippely, M., Park, J.H., Flavell, R. and Bobzin, S. In planta biocatalysis screen of P450s identifies 8-methoxypsoralen as a substrate for the CYP82C subfamily, yielding original chemical structures. Chem. Biol. 15 (2008) 149–156. [PMID: 18291319]
2.	Rajniak, J., Barco, B., Clay, N.K. and Sattely, E.S. A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence. Nature 525 (2015) 376–379. [PMID: 26352477]

[EC 1.14.14.165 created 2018]

1.14.14.166

Accepted name:

(S)-N-methylcanadine 1-hydroxylase

Reaction:

(S)-cis-N-methylcanadine + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-1-hydroxy-cis-N-methylcanadine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of noscapine biosynthesis, click here

Other name(s):

CYP82Y1 (gene name); (S)-N-methylcanadine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (1-hydroxylating)

Systematic name:

(S)-cis-N-methylcanadine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (1-hydroxylating)

Comments:

This cytochrome P-450 (heme-thiolate) enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Dang, T.T. and Facchini, P.J. CYP82Y1 is N-methylcanadine 1-hydroxylase, a key noscapine biosynthetic enzyme in opium poppy. J. Biol. Chem. 289 (2014) 2013–2026. [DOI] [PMID: 24324259]
2.	Li, Y., Li, S., Thodey, K., Trenchard, I., Cravens, A. and Smolke, C.D. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proc. Natl. Acad. Sci. USA 115 (2018) E3922–E3931. [DOI] [PMID: 29610307]

[EC 1.14.14.166 created 2018]

1.14.14.167

Accepted name:

(13S,14R)-13-O-acetyl-1-hydroxy-N-methylcanadine 8-hydroxylase

Reaction:

(13S,14R)-13-O-acetyl-1-hydroxy-cis-N-methylcanadine + [reduced NADPH—hemoprotein reductase] + O₂ = (13S,14R)-13-O-acetyl-1,8-dihydroxy-cis-N-methylcanadine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of noscapine biosynthesis, click here

Other name(s):

CYP82X1 (gene name)

Systematic name:

(13S,14R)-13-O-acetyl-1-hydroxy-cis-N-methylcanadine 8-hydroxylase,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)

Comments:

This cytochrome P-450 (heme-thiolate) enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Dang, T.T., Chen, X. and Facchini, P.J. Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat. Chem. Biol. 11 (2015) 104–106. [DOI] [PMID: 25485687]
2.	Li, Y. and Smolke, C.D. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7:12137 (2016). [DOI] [PMID: 27378283]
3.	Li, Y., Li, S., Thodey, K., Trenchard, I., Cravens, A. and Smolke, C.D. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proc. Natl. Acad. Sci. USA 115 (2018) E3922–E3931. [DOI] [PMID: 29610307]

[EC 1.14.14.167 created 2018]

1.14.14.168

Accepted name:

germacrene A acid 8β-hydroxylase

Reaction:

germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 8β-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of costunolide, eupatolide and 8-epi-inunolide biosynthesis, click here

Glossary:

germacra-1(10),4,11(13)-trien-12-oate = germacrene A acid
8β-hydroxygermacra-1(10),4,11(13)-triene-12-oate = 8β-hydroxygermacrene A acid
inunolide = germacra-1(10),4,11(13)-trien-12,8β-lactone
8-epi-inunolide = germacra-1(10),4,11(13)-trien-12,8α-lactone

Other name(s):

HaG8H; CYP71BL1; CYP71BL6

Systematic name:

germacra-1(10),4,11(13)-trien-12-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8β-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Helianthus annuus (common sunflower). The cyclisation of 8β-hydroxygermacra-1(10),4,11(13)-triene-12-oate to inunolide (12,8β) does not seem to occur spontaneously. The enzyme from Inula hupehensis also forms some 8α-hydroxygermacra-1(10),4,11(13)-triene-12-oate, which spontaneously cyclises to 8-epi-inunolide (12,8α) (cf. EC 1.14.14.170 8-epi-inunolide synthase).

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Frey, M., Schmauder, K., Pateraki, I. and Spring, O. Biosynthesis of eupatolide-A metabolic route for sesquiterpene lactone formation involving the P450 enzyme CYP71DD6. ACS Chem. Biol. 13 (2018) 1536–1543. [PMID: 29758164]
2.	Gou, J., Hao, F., Huang, C., Kwon, M., Chen, F., Li, C., Liu, C., Ro, D.K., Tang, H. and Zhang, Y. Discovery of a non-stereoselective cytochrome P450 catalyzing either 8α- or 8β-hydroxylation of germacrene A acid from the Chinese medicinal plant, Inula hupehensis. Plant J. 93 (2018) 92–106. [PMID: 29086444]

[EC 1.14.14.168 created 2018]

1.14.14.169

Accepted name:

eupatolide synthase

Reaction:

8β-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = eupatolide + [oxidized NADPH—hemoprotein reductase] + 2 H₂O (overall reaction)
(1a) 8β-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 6α,8β-dihydroxygermacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 6α,8β-dihydroxygermacra-1(10),4,11(13)-trien-12-oate = eupatolide + H₂O (spontaneous)

For diagram of costunolide, eupatolide and 8-epi-inunolide biosynthesis, click here

Glossary:

8β-hydroxygermacra-1(10),4,11(13)-triene-12-oate = 8β-hydroxygermacrene A acid
eupatolide = 8β-hydroxygermacra-1(10),4,11(13)-trien-12,6α-lactone

Other name(s):

CYP71DD6; HaES

Systematic name:

8β-hydroxygermacra-1(10),4,11(13)-trien-12-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Helianthus annuus (common sunflower).

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Frey, M., Schmauder, K., Pateraki, I. and Spring, O. Biosynthesis of eupatolide-A metabolic route for sesquiterpene lactone formation involving the P450 enzyme CYP71DD6. ACS Chem. Biol. 13 (2018) 1536–1543. [PMID: 29758164]

[EC 1.14.14.169 created 2018]

1.14.14.170

Accepted name:

8-epi-inunolide synthase

Reaction:

germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 8-epi-inunolide + [oxidized NADPH—hemoprotein reductase] + 2 H₂O (overall reaction)
(1a) germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 8α-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 8α-hydroxygermacra-1(10),4,11(13)-trien-12-oate = 8-epi-inunolide + H₂O (spontaneous)

For diagram of costunolide, eupatolide and 8-epi-inunolide biosynthesis, click here

Glossary:

8-epi-inunolide = germacra-1(10),4,11(13)-trien-12,8α-lactone

Other name(s):

CYP71BL1

Systematic name:

germacra-1(10),4,11(13)-trien-12-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Inula hupehensis. The enzyme also produces 8β-hydroxygermacra-1(10),4,11(13)-triene-12-oate (EC 1.14.14.168, germacrene A acid 8β-hydroxylase).

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Gou, J., Hao, F., Huang, C., Kwon, M., Chen, F., Li, C., Liu, C., Ro, D.K., Tang, H. and Zhang, Y. Discovery of a non-stereoselective cytochrome P450 catalyzing either 8α- or 8β-hydroxylation of germacrene A acid from the Chinese medicinal plant, Inula hupehensis. Plant J. 93 (2018) 92–106. [PMID: 29086444]

[EC 1.14.14.170 created 2018]

1.14.14.171

Accepted name:

β-amyrin 16α-hydroxylase

Reaction:

β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 16α-hydroxy-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of hydroxy-β-amyrin biosynthesis, click here

Glossary:

16α-hydroxy-β-amyrin = olean-12-ene-3β,16α-diol

Other name(s):

CYP87D16

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (16α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the plant Maesa lanceolata (false assegai). Involved in the biosynthesis of maesasaponins. It also acts on some derivatives of β-amyrin such as erythrodiol or oleanolic acid.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Moses, T., Pollier, J., Almagro, L., Buyst, D., Van Montagu, M., Pedreño, M.A., Martins, J.C., Thevelein, J.M. and Goossens, A. Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum. Proc. Natl. Acad. Sci. USA 111 (2014) 1634–1639. [PMID: 24434554]
2.	Moses, T., Pollier, J., Faizal, A., Apers, S., Pieters, L., Thevelein, J.M., Geelen, D. and Goossens, A. Unraveling the triterpenoid saponin biosynthesis of the African shrub Maesa lanceolata. Mol. Plant 8 (2015) 122–135. [DOI] [PMID: 25578277]

[EC 1.14.14.171 created 2019]

1.14.14.172

Accepted name:

3,5,6-trichloropyridin-2-ol monooxygenase

Reaction:

(1) 3,5,6-trichloropyridin-2-ol + FADH₂ + O₂ = 3,6-dichloropyridine-2,5-dione + Cl^- + FAD + H₂O
(2) 3,6-dichloropyridine-2,5-diol + FADH₂ + O₂ = 6-chloro-3-hydroxypyridine-2,5-dione + Cl^- + FAD + H₂O
(3) 6-chloropyridine-2,3,5-triol + FADH₂ + O₂ = 3,6-dihydroxypyridine-2,5-dione + Cl^- + FAD + H₂O

Other name(s):

tcpA (gene name)

Systematic name:

3,5,6-trichloropyridin-2-ol,FADH₂:oxygen oxidoreductase (dechlorinating)

Comments:

The enzyme, characterized from a number of bacterial species, participates in the degradation of 3,5,6-trichloropyridin-2-ol (TCP), a metabolite of the common organophosphorus insecticide chlorpyrifos. The enzyme is a multifunctional flavin-dependent monooxygenase that displaces three chlorine atoms by attacking three different positions in the substrate. Each reaction catalysed by the enzyme displaces a single chlorine and results in formation of a dione, which must be reduced by FADH₂ before the monooxygenase could catalyse the next step. The large amount of FADH₂ that is required is generated by a dedicated flavin reductase (TcpX). cf. EC 1.14.14.173, 2,4,6-trichlorophenol monooxygenase.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Li, J., Huang, Y., Hou, Y., Li, X., Cao, H. and Cui, Z. Novel gene clusters and metabolic pathway involved in 3,5,6-trichloro-2-pyridinol degradation by Ralstonia sp. strain T6. Appl. Environ. Microbiol. 79 (2013) 7445–7453. [PMID: 24056464]
2.	Fang, L., Shi, T., Chen, Y., Wu, X., Zhang, C., Tang, X., Li, Q.X. and Hua, R. Kinetics and catabolic pathways of the insecticide chlorpyrifos, annotation of the degradation genes, and characterization of enzymes TcpA and Fre in Cupriavidus nantongensis X1(T). J. Agric. Food Chem. 67 (2019) 2245–2254. [PMID: 30721044]

[EC 1.14.14.172 created 2020]

1.14.14.173

Accepted name:

2,4,6-trichlorophenol monooxygenase

Reaction:

2,4,6-trichlorophenol + FADH₂ + O₂ = 6-chloro-2-hydroxy-1,4-benzoquinone + 2 Cl^- + FAD (overall reaction)
(1a) 2,4,6-trichlorophenol + FADH₂ + O₂ = 2,6-dichloro-1,4-benzoquinone + Cl^- + FAD + H₂O
(1b) 2,6-dichloro-1,4-benzoquinone + H₂O = 6-chloro-2-hydroxy-1,4-benzoquinone + Cl^-

Other name(s):

tcpA (gene name)

Systematic name:

2,4,6-trichlorophenol,FADH₂:oxygen oxidoreductase (dechlorinating)

Comments:

The enzyme, characterized from Cupriavidus pinatubonensis, participates in the degradation of 2,4,6-trichlorophenol, a compound that has been used for decades as a wood preservative. The enzyme is a multifunctional flavin-dependent monooxygenase that catalyses two different reactions to displace two chlorine atoms, a monooxygenase reaction followed by a hydrolysis reaction that takes advantage of the reactivity of the product of the first reaction, 2,6-dichloro-1,4-benzoquinone [2]. The large amount of FADH₂ that is required is generated by a dedicated flavin reductase (TcpB). cf. EC 1.14.14.172, 3,5,6-trichloropyridin-2-ol monooxygenase.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Louie, T.M., Webster, C.M. and Xun, L. Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation pathway in Ralstonia eutropha JMP134. J. Bacteriol. 184 (2002) 3492–3500. [PMID: 12057943]
2.	Xun, L. and Webster, C.M. A monooxygenase catalyzes sequential dechlorinations of 2,4,6-trichlorophenol by oxidative and hydrolytic reactions. J. Biol. Chem. 279 (2004) 6696–6700. [DOI] [PMID: 14662756]
3.	Hayes, R.P., Webb, B.N., Subramanian, A.K., Nissen, M., Popchock, A., Xun, L. and Kang, C. Structural and catalytic differences between two FADH₂-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134. Int. J. Mol. Sci. 13 (2012) 9769–9784. [DOI] [PMID: 22949829]

[EC 1.14.14.173 created 2020, modified 2022]

1.14.14.174

Accepted name:

geranylhydroquinone 3′′-hydroxylase

Reaction:

geranylhydroquinone + [reduced NADPH—hemoprotein reductase] + O₂ = 3′′-hydroxygeranylhydroquinone + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

3′′-hydroxygeranylhydroquinone = 2-[(2Z)-3-(hydroxymethyl)-7-methylocta-2,6-dien-1-yl]benzene-1,4-diol

Other name(s):

GHQ 3′′-hydroxylase; CYP76B74 (gene name); geranylhydroquinone,NADPH:oxygen oxidoreductase (3′′-hydroxylating)

Systematic name:

geranylhydroquinone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants, where it is part of the biosynthesis pathway of the red naphthoquinone pigment shikonin.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Yamamoto, H., Inoue, K., Li, S.M. and Heide, L. Geranylhydroquinone 3′′-hydroxylase, a cytochrome P-450 monooxygenase from Lithospermum erythrorhizon cell suspension cultures. Planta 210 (2000) 312–317. [DOI] [PMID: 10664138]
2.	Wang, S., Wang, R., Liu, T., Lv, C., Liang, J., Kang, C., Zhou, L., Guo, J., Cui, G., Zhang, Y., Werck-Reichhart, D., Guo, L. and Huang, L. CYP76B74 catalyzes the 3′′-hydroxylation of geranylhydroquinone in shikonin biosynthesis. Plant Physiol. 179 (2019) 402–414. [PMID: 30498024]

[EC 1.14.14.174 created 2010 as EC 1.14.13.116, transferred 2020 to EC 1.14.14.174]

1.14.14.175

Accepted name:

ferruginol synthase

Reaction:

abieta-8,11,13-triene + [reduced NADPH—hemoprotein reductase] + O₂ = ferruginol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietane diterpenoids biosynthesis, click here

Glossary:

ferruginol = abieta-8,11,13-trien-12-ol

Other name(s):

miltiradiene oxidase (incorrect); CYP76AH1; miltiradiene,NADPH:oxygen oxidoreductase (ferruginol forming) (incorrect)

Systematic name:

abieta-8,11,13-triene,[reduced NADPH—hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)

Comments:

A cytochrome P-450 (heme thiolate) enzyme found in some members of the Lamiaceae (mint family). The enzyme from Rosmarinus officinalis (rosemary) is involved in biosynthesis of carnosic acid, while the enzyme from the Chinese medicinal herb Salvia miltiorrhiza is involved in the biosynthesis of the tanshinones, abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components found in the plant.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB

References:

1.	Guo, J., Zhou, Y.J., Hillwig, M.L., Shen, Y., Yang, L., Wang, Y., Zhang, X., Liu, W., Peters, R.J., Chen, X., Zhao, Z.K. and Huang, L. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. Proc. Natl. Acad. Sci. USA 110 (2013) 12108–12113. [DOI] [PMID: 23812755]
2.	Zi, J. and Peters, R.J. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae. Org. Biomol. Chem. 11 (2013) 7650–7652. [DOI] [PMID: 24108414]
3.	Bozic, D., Papaefthimiou, D., Bruckner, K., de Vos, R.C., Tsoleridis, C.A., Katsarou, D., Papanikolaou, A., Pateraki, I., Chatzopoulou, F.M., Dimitriadou, E., Kostas, S., Manzano, D., Scheler, U., Ferrer, A., Tissier, A., Makris, A.M., Kampranis, S.C. and Kanellis, A.K. Towards elucidating carnosic acid biosynthesis in Lamiaceae: functional characterization of the three first steps of the pathway in Salvia fruticosa and Rosmarinus officinalis. PLoS One 10:e0124106 (2015). [DOI] [PMID: 26020634]

[EC 1.14.14.175 created 2014 as EC 1.14.13.190, modified 2015, transferred 2020 to EC 1.14.14.175]

1.14.14.176

Accepted name:

taxadiene 5α-hydroxylase

Reaction:

taxa-4,11-diene + [reduced NADPH—hemoprotein reductase] + O₂ = taxa-4(20),11-dien-5α-ol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of taxadiene hydroxylation, click here

Systematic name:

taxa-4,11-diene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (5α-hydroxylating)

Comments:

This microsomal cytochrome-P-450 (heme-thiolate) enzyme is involved in the biosynthesis of the diterpenoid antineoplastic drug taxol (paclitaxel). The reaction includes rearrangement of the 4(5)-double bond to a 4(20)-double bond, possibly through allylic oxidation.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9035-51-2

References:

1.	Hefner, J., Rubenstein, S.M., Ketchum, R.E., Gibson, D.M., Williams, R.M. and Croteau, R. Cytochrome P₄₅₀-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5α-ol: the first oxygenation step in taxol biosynthesis. Chem. Biol. 3 (1996) 479–489. [DOI] [PMID: 8807878]

[EC 1.14.14.176 created 2002 as 1.14.99.37, transferred 2020 to EC 1.14.14.176]

1.14.14.177

Accepted name:

ultra-long-chain fatty acid ω-hydroxylase

Reaction:

an ultra-long-chain fatty acid + [reduced NADPH—hemoprotein reductase] + O₂ = an ultra-long-chain ω-hydroxy fatty acid + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

CYP4F22 (gene name)

Systematic name:

ultra-long-chain fatty acid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxylating)

Comments:

The enzyme, which is expressed in the epidermis of mammals, catalyses the ω-hydroxylation of ultra-long-chain fatty acids (C₂₈ to C₃₆). The products are incorporated into acylceramides, epidermis-specific ceramide species that are very important for skin barrier formation.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Ohno, Y., Nakamichi, S., Ohkuni, A., Kamiyama, N., Naoe, A., Tsujimura, H., Yokose, U., Sugiura, K., Ishikawa, J., Akiyama, M. and Kihara, A. Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation. Proc. Natl. Acad. Sci. USA 112 (2015) 7707–7712. [DOI] [PMID: 26056268]

[EC 1.14.14.177 created 2021]

1.14.14.178

Accepted name:

steroid 22S-hydroxylase

Reaction:

(1) a C₂₇-steroid + O₂ + [reduced NADPH—hemoprotein reductase] = a (22S)-22-hydroxy-C₂₇-steroid + 2 H₂O + [oxidized NADPH—hemoprotein reductase]
(2) a C₂₈-steroid + O₂ + [reduced NADPH—hemoprotein reductase] = a (22S)-22-hydroxy-C₂₈-steroid + 2 H₂O + [oxidized NADPH—hemoprotein reductase]
(3) a C₂₉-steroid + O₂ + [reduced NADPH—hemoprotein reductase] = a (22S)-22-hydroxy-C₂₉-steroid + 2 H₂O + [oxidized NADPH—hemoprotein reductase]

Other name(s):

CYP90B1 (gene name); DWF4 (gene name); steroid C-22 hydroxylase

Systematic name:

steroid,NADPH—hemoprotein reductase:oxygen 22S-oxidoreductase (hydroxylating)

Comments:

This plant cytochrome P-450 (heme thiolate) enzyme participates in the biosynthesis of brassinosteroids. While in vivo substrates include C₂₈-steroids such as campestanol, campesterol, and 6-oxocampestanol, the enzyme is able to catalyse the C-22 hydroxylation of a variety of C₂₇, C₂₈ and C₂₉ steroids.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Asami, T., Mizutani, M., Fujioka, S., Goda, H., Min, Y.K., Shimada, Y., Nakano, T., Takatsuto, S., Matsuyama, T., Nagata, N., Sakata, K. and Yoshida, S. Selective interaction of triazole derivatives with DWF4, a cytochrome P450 monooxygenase of the brassinosteroid biosynthetic pathway, correlates with brassinosteroid deficiency in planta. J. Biol. Chem. 276 (2001) 25687–25691. [DOI] [PMID: 11319239]
2.	Choe, S., Fujioka, S., Noguchi, T., Takatsuto, S., Yoshida, S. and Feldmann, K.A. Overexpression of DWARF4 in the brassinosteroid biosynthetic pathway results in increased vegetative growth and seed yield in Arabidopsis. Plant J. 26 (2001) 573–582. [DOI] [PMID: 11489171]
3.	Asami, T., Mizutani, M., Shimada, Y., Goda, H., Kitahata, N., Sekimata, K., Han, S.Y., Fujioka, S., Takatsuto, S., Sakata, K. and Yoshida, S. Triadimefon, a fungicidal triazole-type P450 inhibitor, induces brassinosteroid deficiency-like phenotypes in plants and binds to DWF4 protein in the brassinosteroid biosynthesis pathway. Biochem. J. 369 (2003) 71–76. [DOI] [PMID: 12350224]
4.	Fujita, S., Ohnishi, T., Watanabe, B., Yokota, T., Takatsuto, S., Fujioka, S., Yoshida, S., Sakata, K. and Mizutani, M. Arabidopsis CYP90B1 catalyses the early C-22 hydroxylation of C₂₇, C₂₈ and C₂₉ sterols. Plant J. 45 (2006) 765–774. [DOI] [PMID: 16460510]
5.	Ohnishi, T., Watanabe, B., Sakata, K. and Mizutani, M. CYP724B2 and CYP90B3 function in the early C-22 hydroxylation steps of brassinosteroid biosynthetic pathway in tomato. Biosci. Biotechnol. Biochem. 70 (2006) 2071–2080. [DOI] [PMID: 16960392]

[EC 1.14.14.178 created 2022]

1.14.14.179

Accepted name:

brassinosteroid 6-oxygenase

Reaction:

6-deoxocastasterone + 2 O₂ + 2 [reduced NADPH—hemoprotein reductase] = castasterone + 3 H₂O + 2 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) 6-deoxocastasterone + O₂ + [reduced NADPH—hemoprotein reductase] = 6α-hydroxy-6-deoxocastasterone + H₂O + [oxidized NADPH—hemoprotein reductase]
(1b) 6α-hydroxy-6-deoxocastasterone + O₂ + [reduced NADPH—hemoprotein reductase] = castasterone + 2 H₂O + [oxidized NADPH—hemoprotein reductase]

For diagram of brassinolide biosynthesis, click here

Other name(s):

CYP85A1 (gene name); CYP85A2 (gene name); brassinosteroid 6-oxidase

Systematic name:

6-deoxocastasterone,NADPH—hemoprotein reductase:oxygen 6-oxidoreductase (castasterone-forming)

Comments:

This cytochrome P-450 (heme thiolate) plant enzyme catalyses the C-6 hydoxylation of several brassinosteroid biosynthesis intermediates, and the further oxidation of the hydroxyl group to an oxo group. Substrates include 6-deoxocastasterone, 6-deoxotyphasterol, 3-dehydro-6-deoxoteasterone, and 6-deoxoteasterone. The CYP85A2 isozyme of Arabidopsis thaliana (but not the CYP85A1 isozyme) also catalyses the activity of EC 1.14.14.180, brassinolide synthase.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Shimada, Y., Fujioka, S., Miyauchi, N., Kushiro, M., Takatsuto, S., Nomura, T., Yokota, T., Kamiya, Y., Bishop, G.J. and Yoshida, S. Brassinosteroid-6-oxidases from Arabidopsis and tomato catalyze multiple C-6 oxidations in brassinosteroid biosynthesis. Plant Physiol. 126 (2001) 770–779. [DOI] [PMID: 11402205]
2.	Perez-Espana, V.H., Sanchez-Leon, N. and Vielle-Calzada, J.P. CYP85A1 is required for the initiation of female gametogenesis in Arabidopsis thaliana. Plant Signal Behav. 6 (2011) 321–326. [DOI] [PMID: 21364326]

[EC 1.14.14.179 created 2022]

1.14.14.180

Accepted name:

brassinolide synthase

Reaction:

castasterone + O₂ + [reduced NADPH—hemoprotein reductase] = brassinolide + 2 H₂O + [oxidized NADPH—hemoprotein reductase]

For diagram of brassinolide biosynthesis, click here

Other name(s):

CYP85A2 (gene name); CYP85A3 (gene name)

Systematic name:

castasterone,NADPH—hemoprotein reductase:oxygen oxidoreductase (lactonizing, brassinolide-forming)

Comments:

This cytochrome P-450 (heme thiolate) plant enzyme catalyses the lactonization of several brassinosteroids, including castasterone, teasterone, and typhasterol. The CYP85A2 enzyme of Arabidopsis thaliana also catalyses the activity of EC 1.14.14.179, brassinosteroid 6-oxygenase.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Nomura, T., Kushiro, T., Yokota, T., Kamiya, Y., Bishop, G.J. and Yamaguchi, S. The last reaction producing brassinolide is catalyzed by cytochrome P-450s, CYP85A3 in tomato and CYP85A2 in Arabidopsis. J. Biol. Chem. 280 (2005) 17873–17879. [DOI] [PMID: 15710611]
2.	Kim, T.W., Hwang, J.Y., Kim, Y.S., Joo, S.H., Chang, S.C., Lee, J.S., Takatsuto, S. and Kim, S.K. Arabidopsis CYP85A2, a cytochrome P450, mediates the Baeyer-Villiger oxidation of castasterone to brassinolide in brassinosteroid biosynthesis. Plant Cell 17 (2005) 2397–2412. [DOI] [PMID: 16024588]
3.	Katsumata, T., Hasegawa, A., Fujiwara, T., Komatsu, T., Notomi, M., Abe, H., Natsume, M. and Kawaide, H. Arabidopsis CYP85A2 catalyzes lactonization reactions in the biosynthesis of 2-deoxy-7-oxalactone brassinosteroids. Biosci. Biotechnol. Biochem. 72 (2008) 2110–2117. [DOI] [PMID: 18685225]

[EC 1.14.14.180 created 2022]

1.14.14.181

Accepted name:

sulfoquinovose monooxygenase

Reaction:

6-sulfo-D-quinovose + FMNH₂ + O₂ = 6-dehydro-D-glucose + FMN + sulfite + H₂O

Glossary:

D-quinovose = 6-deoxy-D-glucopyranose
6-dehydro-D-glucose = 6-oxo-D-quinovose

Other name(s):

6-deoxy-6-sulfo-D-glucose monooxygenase; smoC (gene name); squD (gene name)

Systematic name:

6-sulfo-D-quinovose,FMNH₂:oxygen oxidoreductase

Comments:

The enzyme, characterized from the bacteria Agrobacterium fabrum and Rhizobium oryzae, is involved in a D-sulfoquinovose degradation pathway. FMNH₂ is provided by an associated FMN reductase [SmoA, EC 1.5.1.42, FMN reductase (NADH)].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB

References:

Liu, J., Wei, Y., Ma, K., An, J., Liu, X., Liu, Y., Ang, E.L., Zhao, H. and Zhang, Y. Mechanistically diverse pathways for sulfoquinovose degradation in bacteria. ACS Catal. 11 (2021) 14740–14750. [DOI]

Sharma, M., Lingford, J.P., Petricevic, M., Snow, A.J.D., Zhang, Y., Jarva, M.A., Mui, J.W., Scott, N.E., Saunders, E.C., Mao, R., Epa, R., da Silva, B.M., Pires, D.E.V., Ascher, D.B., McConville, M.J., Davies, G.J., Williams, S.J. and Goddard-Borger, E.D. Oxidative desulfurization pathway for complete catabolism of sulfoquinovose by bacteria. Proc. Natl. Acad. Sci. USA 119 (2022) e2116022119. [DOI] [PMID: 35074914]

[EC 1.14.14.181 created 20022]

1.14.14.182

Accepted name:

taxoid 7β-hydroxylase

Reaction:

(1) taxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 7β-hydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 2α-hydroxytaxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α,7β-dihydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

taxusin = taxa-4(20),11-diene-5α,9α,10β,13α-tetrayl tetraacetate

Systematic name:

taxusin, [reduced NADPH—hemoprotein reductase]:oxygen 7-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein from the yew tree Taxus cuspidata. Does not act on earlier intermediates in taxol biosynthesis.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Chau, M., Jennewein, S., Walker, K. and Croteau, R. Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7β-hydroxylase. Chem. Biol. 11 (2004) 663–672. [DOI] [PMID: 15157877]
2.	Chau, M. and Croteau, R. Molecular cloning and characterization of a cytochrome P450 taxoid 2α-hydroxylase involved in taxol biosynthesis. Arch. Biochem. Biophys. 427 (2004) 48–57. [DOI] [PMID: 15178487]

[EC 1.14.14.182 created 2012 as EC 1.14.13.147, transferred 2022 to EC 1.14.14.182]

1.14.14.183

Accepted name:

taxoid 2α-hydroxylase

Reaction:

(1) taxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α-hydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 7β-hydroxytaxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α,7β-dihydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

taxusin = taxa-4(20),11-diene-5α,9α,10β,13α-tetrayl tetraacetate

Systematic name:

taxusin, [reduced NADPH—hemoprotein reductase]:oxygen 2-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein from the yew tree Taxus cuspidata. Does not act on earlier intermediates in taxol biosynthesis.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Chau, M., Jennewein, S., Walker, K. and Croteau, R. Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7β-hydroxylase. Chem. Biol. 11 (2004) 663–672. [DOI] [PMID: 15157877]
2.	Chau, M. and Croteau, R. Molecular cloning and characterization of a cytochrome P450 taxoid 2α-hydroxylase involved in taxol biosynthesis. Arch. Biochem. Biophys. 427 (2004) 48–57. [DOI] [PMID: 15178487]

[EC 1.14.14.183 created 2022]

1.14.14.184

Accepted name:

5-dehydro-6-demethoxyfumagillol synthase

Reaction:

(+)-exo-β-bergamotene + 2 [reduced NADPH—hemoprotein reductase] + 3 O₂ = 5-dehydro-6-demethoxyfumagillol + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) (+)-exo-β-bergamotene + [reduced NADPH—hemoprotein reductase] + O₂ = (5R)-hydroxy-(+)-exo-β-bergamotene + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) (5R)-hydroxy-(+)-exo-β-bergamotene + O₂ = (3S)-3-[2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-4-methylidenecyclohexan-1-one + H₂O
(1c) (3S)-3-[2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-4-methylidenecyclohexan-1-one + [reduced NADPH—hemoprotein reductase] + O₂ = 5-dehydro-6-demethoxyfumagillol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of reaction, click here and for diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(+)-exo-β-bergamotene = β-trans-bergamotene = (1S,5S,6R)-6-methyl-2-methylidene-6-(4-methylpent-3-enyl)bicyclo[3.1.1]heptane
fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
fumagillin = (2E,4E,6E,8E)-10-({(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]oct-6-yl}oxy)-10-oxodeca-2,4,6,8-tetraenoate

Other name(s):

fumagillin multifunctional cytochrome P450 monooxygenase; Fma-P450; fmaG (gene name)

Systematic name:

(+)-exo-β-bergamotene,[reduced NADPH—hemoprotein reductase] oxidoreductase (5-dehydro-6-demethoxyfumagillol-producing)

Comments:

The enzyme, characterized from the mold Aspergillus fumigatus, catalyses a complex transformation comprising hydroxylation, bicyclic ring-opening, and two epoxidations, generating the sesquiterpenoid core skeleton of fumagillin.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426–4436. [DOI] [PMID: 24568283]

[EC 1.14.14.184 created 2022]

1.14.14.185

Accepted name:

taxane 9α-hydroxylase

Reaction:

5,20-epoxytax-11-en-4α-ol + [reduced NADPH—hemoprotein reductase] + O₂ = 5,20-epoxytax-11-ene-4α,9α-diol + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

taxoid 9α hydroxylase; CYP725A22; T9αOH

Systematic name:

5,20-epoxytax-11-en-4α-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (9α-hydroxylating)

Comments:

The enzyme is active in the biosynthetic pathway of paclitaxel (Taxol) in Taxus species (yew).

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Zhang, Y., Wiese, L., Fang, H., Alseekh, S., Perez de Souza, L., Scossa, F., Molloy, J., Christmann, M. and Fernie, A.R. Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis. Mol. Plant 16 (2023) 1951–1961. [DOI] [PMID: 37897038]

[EC 1.14.14.185 created 2024]