Accepted name: flavanone 4-reductase
Reaction: (2S)-flavan-4-ol + NADP+ = (2S)-flavanone + NADPH + H+
Systematic name: (2S)-flavan-4-ol:NADP+ 4-oxidoreductase
Comments: Involved in the biosynthesis of 3-deoxyanthocyanidins from flavanones such as naringenin or eriodictyol.
1.  Stich, K. and Forkmann, G. Biosynthesis of 3-deoxyanthocyanins with flower extracts from Sinningia cardinalis. Phytochemistry 27 (1988) 785–789.
[EC created 1992]
Accepted name: flavanone 3-dioxygenase
Reaction: a (2S)-flavan-4-one + 2-oxoglutarate + O2 = a (2R,3R)-dihydroflavonol + succinate + CO2
Other name(s): naringenin 3-hydroxylase; flavanone 3-hydroxylase; flavanone 3β-hydroxylase; flavanone synthase I; (2S)-flavanone 3-hydroxylase; naringenin,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating); F3H; flavanone,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Systematic name: (2S)-flavan-4-one,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Comments: Requires Fe2+ and ascorbate. This plant enzyme catalyses an early step in the flavonoid biosynthesis pathway, leading to the production of flavanols and anthocyanins. Substrates include (2S)-naringenin, (2S)-eriodictyol, (2S)-dihydrotricetin and (2S)-pinocembrin. Some enzymes are bifuctional and also catalyse EC, flavonol synthase.
1.  Forkmann, G., Heller, W. and Grisebach, H. Anthocyanin biosynthesis in flowers of Matthiola incana flavanone 3- and flavonoid 3′-hydroxylases. Z. Naturforsch. C: Biosci. 35 (1980) 691–695.
2.  Charrier, B., Coronado, C., Kondorosi, A. and Ratet, P. Molecular characterization and expression of alfalfa (Medicago sativa L.) flavanone-3-hydroxylase and dihydroflavonol-4-reductase encoding genes. Plant Mol. Biol. 29 (1995) 773–786. [PMID: 8541503]
3.  Pelletier, M.K. and Shirley, B.W. Analysis of flavanone 3-hydroxylase in Arabidopsis seedlings. Coordinate regulation with chalcone synthase and chalcone isomerase. Plant Physiol. 111 (1996) 339–345. [PMID: 8685272]
4.  Wellmann, F., Matern, U. and Lukačin, R. Significance of C-terminal sequence elements for Petunia flavanone 3β-hydroxylase activity. FEBS Lett. 561 (2004) 149–154. [PMID: 15013767]
5.  Jin, Z., Grotewold, E., Qu, W., Fu, G. and Zhao, D. Cloning and characterization of a flavanone 3-hydroxylase gene from Saussurea medusa. DNA Seq 16 (2005) 121–129. [PMID: 16147863]
6.  Shen, G., Pang, Y., Wu, W., Deng, Z., Zhao, L., Cao, Y., Sun, X. and Tang, K. Cloning and characterization of a flavanone 3-hydroxylase gene from Ginkgo biloba. Biosci Rep 26 (2006) 19–29. [PMID: 16779664]
[EC created 1983, modified 1989, modified 2004, modified 2016]
Transferred entry: flavone synthase. Now EC, flavone synthase
[EC created 2004, deleted 2018]
Transferred entry: flavonol synthase. Now EC, flavonol synthase
[EC created 2004, deleted 2018]
Transferred entry: flavonoid 3′-monooxygenase. Now EC, flavonoid 3′-monooxygenase.
[EC created 1983, deleted 2018]
Transferred entry: flavanoid 3,5-hydroxylase. Now EC, flavanoid 3,5-hydroxylase
[EC created 2004, deleted 2018]
Transferred entry: 8-dimethylallylnaringenin 2-hydroxylase. Now EC, 8-dimethylallylnaringenin 2-hydroxylase
[EC created 2007, deleted 2018]
Transferred entry: 2-hydroxyisoflavanone synthase. Now EC, 2-hydroxyisoflavanone synthase
[EC created 2011, modified 2013, deleted 2018]
Transferred entry: geraniol 8-hydroxylase. Now EC, geraniol 8-hydroxylase
[EC created 2012, deleted 2018]
Accepted name: flavanoid 3′,5′-hydroxylase
Reaction: a flavanone + 2 [reduced NADPH—hemoprotein reductase] + 2 O2 = a 3′,5′-dihydroxyflavanone + 2 [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) a flavanone + [reduced NADPH—hemoprotein reductase] + O2 = a 3′-hydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) a 3′-hydroxyflavanone + [reduced NADPH—hemoprotein reductase] + O2 = a 3′,5′-dihydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): flavonoid 3′,5′-hydroxylase
Systematic name: flavanone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′,5′-dihydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein found in plants. The 3′,5′-dihydroxyflavanone is formed via the 3′-hydroxyflavanone. In Petunia hybrida the enzyme acts on naringenin, eriodictyol, dihydroquercetin (taxifolin) and dihydrokaempferol (aromadendrin). The enzyme catalyses the hydroxylation of 5,7,4′-trihydroxyflavanone (naringenin) at either the 3′ position to form eriodictyol or at both the 3′ and 5′ positions to form 5,7,3′,4′,5′-pentahydroxyflavanone (dihydrotricetin). The enzyme also catalyses the hydroxylation of 3,5,7,3′,4′-pentahydroxyflavanone (taxifolin) at the 5′ position, forming ampelopsin.
1.  Menting, J., Scopes, R.K. and Stevenson, T.W. Characterization of flavonoid 3′,5′-hydroxylase in microsomal membrane fraction of Petunia hybrida flowers. Plant Physiol. 106 (1994) 633–642. [PMID: 12232356]
2.  Shimada, Y., Nakano-Shimada, R., Ohbayashi, M., Okinaka, Y., Kiyokawa, S. and Kikuchi, Y. Expression of chimeric P450 genes encoding flavonoid-3′, 5′-hydroxylase in transgenic tobacco and petunia plants1. FEBS Lett. 461 (1999) 241–245. [PMID: 10567704]
3.  de Vetten, N., ter Horst, J., van Schaik, H.P., de Boer, A., Mol, J. and Koes, R. A cytochrome b5 is required for full activity of flavonoid 3′, 5′-hydroxylase, a cytochrome P450 involved in the formation of blue flower colors. Proc. Natl. Acad. Sci. USA 96 (1999) 778–783. [PMID: 9892710]
[EC created 2004 as EC, transferred 2018 to EC]
Accepted name: flavonoid 3′-monooxygenase
Reaction: a flavonoid + [reduced NADPH—hemoprotein reductase] + O2 = a 3′-hydroxyflavonoid + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): CYP75B1 (gene name); flavonoid 3′-hydroxylase; flavonoid 3-hydroxylase (incorrect); NADPH:flavonoid-3′-hydroxylase (incorrect); flavonoid 3-monooxygenase (incorrect)
Systematic name: flavonoid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein found in plants. Acts on a number of flavonoids, including the flavanone naringenin and the flavone apigenin. Does not act on 4-coumarate or 4-coumaroyl-CoA.
1.  Forkmann, G., Heller, W. and Grisebach, H. Anthocyanin biosynthesis in flowers of Matthiola incana flavanone 3- and flavonoid 3′-hydroxylases. Z. Naturforsch. C: Biosci. 35 (1980) 691–695.
2.  Brugliera, F., Barri-Rewell, G., Holton, T.A. and Mason, J.G. Isolation and characterization of a flavonoid 3′-hydroxylase cDNA clone corresponding to the Ht1 locus of Petunia hybrida. Plant J. 19 (1999) 441–451. [PMID: 10504566]
3.  Schoenbohm, C., Martens, S., Eder, C., Forkmann, G. and Weisshaar, B. Identification of the Arabidopsis thaliana flavonoid 3′-hydroxylase gene and functional expression of the encoded P450 enzyme. Biol. Chem. 381 (2000) 749–753. [PMID: 11030432]
[EC created 1983 as EC, transferred 2018 to EC]
Accepted name: geraniol 8-hydroxylase
Reaction: geraniol + [reduced NADPH—hemoprotein reductase] + O2 = (6E)-8-hydroxygeraniol + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): CYP76B6 (gene name); G10H (gene name)
Systematic name: geraniol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)
Comments: A cytochrome P-450 (heme thiolate) protein found in plants. Also hydroxylates nerol and citronellol, cf. EC, linalool 8-monooxygenase. The recommended numbering of geraniol gives 8-hydroxygeraniol as the product rather than 10-hydroxygeraniol as used by references 1-3. See prenol nomenclature Pr-1. The cloned enzyme also catalysed, but less efficiently, the 3′-hydroxylation of naringenin (cf. EC, flavonoid 3′-monooxygenase) [3].
1.  Collu, G., Unver, N., Peltenburg-Looman, A.M., van der Heijden, R., Verpoorte, R. and Memelink, J. Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett. 508 (2001) 215–220. [PMID: 11718718]
2.  Wang, J., Liu, Y., Cai, Y., Zhang, F., Xia, G. and Xiang, F. Cloning and functional analysis of geraniol 10-hydroxylase, a cytochrome P450 from Swertia mussotii Franch. Biosci. Biotechnol. Biochem. 74 (2010) 1583–1590. [PMID: 20699579]
3.  Sung, P.H., Huang, F.C., Do, Y.Y. and Huang, P.L. Functional expression of geraniol 10-hydroxylase reveals its dual function in the biosynthesis of terpenoid and phenylpropanoid. J. Agric. Food Chem. 59 (2011) 4637–4643. [PMID: 21504162]
[EC created 2012 as EC, transferred 2018 to EC]
Accepted name: 2-hydroxyisoflavanone synthase
Reaction: (1) liquiritigenin + O2 + [reduced NADPH—hemoprotein reductase] = 2,4′,7-trihydroxyisoflavanone + H2O + [oxidized NADPH—hemoprotein reductase]
(2) (2S)-naringenin + O2 + [reduced NADPH—hemoprotein reductase] = 2,4′,5,7-tetrahydroxyisoflavanone + H2O + [oxidized NADPH—hemoprotein reductase]
Glossary: liquiritigenin = 4′,7-dihydroxyflavanone
(2S)-naringenin = 4′,5,7-dihydroxyflavanone
2,4′,5,7-tetrahydroxyisoflavanone = 2-hydroxy-2,3-dihydrogenistein
Other name(s): CYP93C; IFS; isoflavonoid synthase
Systematic name: liquiritigenin, [reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating, aryl migration)
Comments: A cytochrome P-450 (heme thiolate) protein found in plants. The reaction involves the migration of the 2-phenyl group of the flavanone to the 3-position of the isoflavanone. The 2-hydroxyl group is derived from the oxygen molecule. EC, 2-hydroxyisoflavanone dehydratase, acts on the products with loss of water and formation of genistein and daidzein, respectively.
1.  Kochs, G. and Grisebach, H. Enzymic synthesis of isoflavones. Eur. J. Biochem. 155 (1986) 311–318. [PMID: 3956488]
2.  Hashim, M.F., Hakamatsuka, T., Ebizuka, Y. and Sankawa, U. Reaction mechanism of oxidative rearrangement of flavanone in isoflavone biosynthesis. FEBS Lett. 271 (1990) 219–222. [PMID: 2226805]
3.  Steele, C. L., Gijzen, M., Qutob, D. and Dixon, R.A. Molecular characterization of the enzyme catalyzing the aryl migration reaction of isoflavonoid biosynthesis in soybean. Arch. Biochem. Biophys. 367 (1999) 146–150. [PMID: 10375412]
4.  Sawada, Y., Kinoshita, K., Akashi, T., Aoki, T. and Ayabe, S. Key amino acid residues required for aryl migration catalysed by the cytochrome P450 2-hydroxyisoflavanone synthase. Plant J. 31 (2002) 555–564. [PMID: 12207646]
5.  Sawada, Y. and Ayabe, S. Multiple mutagenesis of P450 isoflavonoid synthase reveals a key active-site residue. Biochem. Biophys. Res. Commun. 330 (2005) 907–913. [PMID: 15809082]
[EC created 2011 as EC, modified 2013, transferred 2018 to EC]
Accepted name: 8-dimethylallylnaringenin 2′-hydroxylase
Reaction: sophoraflavanone B + [reduced NADPH—hemoprotein reductase] + O2 = leachianone G + [oxidized NADPH—hemoprotein reductase] + H2O
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 (naringenin 8-dimethylallyltransferase) and EC (leachianone G 2′′-dimethylallyltransferase), this enzyme forms part of the sophoraflavanone G biosynthetic pathway.
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. [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. [PMID: 14551337]
[EC created 2007 asEC, transferred 2018 to EC]
Accepted name: flavanone 2-hydroxylase
Reaction: a flavanone + [reduced NADPH—hemoprotein reductase] + O2 = a 2-hydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H2O
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.
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. [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 created 2018. EC created 2004 as EC, transferred 2018 to EC, transferred 2018 to EC]
Accepted name: flavone synthase I
Reaction: a flavanone + 2-oxoglutarate + O2 = a flavone + succinate + CO2 + H2O
Other name(s): FNSI (gene name)
Systematic name: flavanone,2-oxoglutarate:oxygen oxidoreductase (dehydrating)
Comments: The enzyme, which has been found in rice and in members of the Apiaceae (a plant family), is a member of the 2-oxoglutarate-dependent dioxygenases, and requires ascorbate and Fe2+ for full activity.
1.  Martens, S., Forkmann, G., Matern, U. and Lukačin, R. Cloning of parsley flavone synthase I. Phytochemistry 58 (2001) 43–46. [PMID: 11524111]
2.  Lukačin, R., Matern, U., Junghanns, K.T., Heskamp, M.L., Britsch, L., Forkmann, G. and Martens, S. Purification and antigenicity of flavone synthase I from irradiated parsley cells. Arch. Biochem. Biophys. 393 (2001) 177–183. [PMID: 11516175]
3.  Martens, S., Forkmann, G., Britsch, L., Wellmann, F., Matern, U. and Lukačin, R. Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett. 544 (2003) 93–98. [PMID: 12782296]
[EC created 2004 as EC, transferred 2018 to EC]
Accepted name: flavonol synthase
Reaction: a dihydroflavonol + 2-oxoglutarate + O2 = a flavonol + succinate + CO2 + H2O
Other name(s): FLS (gene name)
Systematic name: dihydroflavonol,2-oxoglutarate:oxygen oxidoreductase
Comments: In addition to the desaturation of (2R,3R)-dihydroflavonols to flavonols, the enzyme from Citrus unshiu (satsuma mandarin) also has a non-specific activity that trans-hydroxylates the flavanones (2S)-naringenin and the unnatural (2R)-naringenin at C-3 to kaempferol and (2R,3R)-dihydrokaempferol, respectively [2]. Requires Fe2+.
1.  Wellmann, F., Lukačin, R., Moriguchi, T., Britsch, L., Schiltz, E. and Matern, U. Functional expression and mutational analysis of flavonol synthase from Citrus unshiu. Eur. J. Biochem. 269 (2002) 4134–4142. [PMID: 12180990]
2.  Lukačin, R., Wellmann, F., Britsch, L., Martens, S. and Matern, U. Flavonol synthase from Citrus unshiu is a bifunctional dioxygenase. Phytochemistry 62 (2003) 287–292. [PMID: 12620339]
3.  Martens, S., Forkmann, G., Britsch, L., Wellmann, F., Matern, U. and Lukačin, R. Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett. 544 (2003) 93–98. [PMID: 12782296]
4.  Turnbull, J.J., Nakajima, J., Welford, R.W., Yamazaki, M., Saito, K. and Schofield, C.J. Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis: anthocyanidin synthase, flavonol synthase, and flavanone 3β-hydroxylase. J. Biol. Chem. 279 (2004) 1206–1216. [PMID: 14570878]
[EC created 2004 as EC, transferred 2018 to EC]
Accepted name: monoprenyl isoflavone epoxidase
Reaction: 7-O-methylluteone + NADPH + H+ + O2 = dihydrofurano derivatives + NADP+ + H2O
Glossary: luteone = 3-(2,4-dihydroxyphenyl)-5,7-dihydroxy-6-(3-methyl-2-butenyl)-4H-1-benzopyran-4-one
naringenin = 4′,5,7-trihydroxyflavan-4-one
Other name(s): monoprenyl isoflavone monooxygenase; 7-O-methylluteone:O2 oxidoreductase; 7-O-methylluteone,NADPH:O2 oxidoreductase
Systematic name: 7-O-methylluteone,NADPH:oxygen oxidoreductase
Comments: A flavoprotein (FAD) with high specificity for monoprenyl isoflavone. The product of the prenyl epoxidation reaction contains an oxygen atom derived from O2, but not from H2O. It is slowly and non-enzymically converted into the corresponding dihydrofurano derivative. The enzyme in the fungus Botrytis cinerea is induced by the substrate analogue, 6-prenylnaringenin.
1.  Tanaka, M. and Tahara, S. FAD-dependent epoxidase as a key enzyme in fungal metabolism of prenylated flavonoids. Phytochemistry 46 (1997) 433–439.
[EC created 2000]
Accepted name: isoflavone 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 4′-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 4′-methoxyisoflavone
Other name(s): 4′-hydroxyisoflavone methyltransferase; isoflavone methyltransferase; isoflavone O-methyltransferase
Systematic name: S-adenosyl-L-methionine:4′-hydroxyisoflavone 4′-O-methyltransferase
Comments: Requires Mg2+ for activity. The enzyme catalyses the methylation of daidzein and genistein. It does not methylate naringenin, apigenin, luteolin or kaempferol.
1.  Wengenmayer, H., Ebel, J. and Grisebach, H. Purification and properties of a S-adenosylmethionine: isoflavone 4′-O-methyltransferase from cell suspension cultures of Cicer arietinum L. Eur. J. Biochem. 50 (1974) 135–143. [PMID: 4452353]
[EC created 1976, modified 2011]
Accepted name: apigenin 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + apigenin = S-adenosyl-L-homocysteine + acacetin
Glossary: apigenin = 4′,5,7-trihydroxyflavone
acacetin = 4′-methoxy-5,7-dihydroxyflavone
naringenin = 4′,5,7-trihydroxyflavan-4-one
Other name(s): flavonoid O-methyltransferase; flavonoid methyltransferase; S-adenosyl-L-methionine:5,7,4′-trihydroxyflavone 4′-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:apigenin 4′-O-methyltransferase
Comments: Converts apigenin into acacetin. Naringenin can also act as an acceptor, but more slowly.
1.  Kuroki, G. and Poulton, J.E. The para-O-methylation of apigenin to acacetin by cell-free extracts of Robinia pseudoacacia L. Z. Naturforsch. C: Biosci. 36 (1981) 916–920.
[EC created 1984]
Accepted name: flavonoid 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 4′-hydroxyflavanone = S-adenosyl-L-homocysteine + a 4′-methoxyflavanone
Glossary: naringenin = 4′,5,7-trihydroxyflavan-4-one
Other name(s): SOMT-2; 4′-hydroxyisoflavone methyltransferase
Systematic name: S-adenosyl-L-methionine:flavonoid 4′-O-methyltransferase
Comments: The enzyme catalyses the 4′-methylation of naringenin. In vitro it catalyses the 4′-methylation of apigenin, quercetin, daidzein and genistein.
1.  Kim, D.H., Kim, B.G., Lee, Y., Ryu, J.Y., Lim, Y., Hur, H.G. and Ahn, J.H. Regiospecific methylation of naringenin to ponciretin by soybean O-methyltransferase expressed in Escherichia coli. J. Biotechnol. 119 (2005) 155–162. [PMID: 15961179]
[EC created 2011]
Accepted name: naringenin 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (2S)-naringenin = S-adenosyl-L-homocysteine + (2S)-sakuranetin
Glossary: (2S)-naringenin = (2S)-5,7,4′-trihydroxyflavan-4-one
(2S)-sakuranetin = (2S)-5,4′-dihydroxy-7-methoxyflavan-4-one
Other name(s): NOMT
Systematic name: S-adenosyl-L-methionine:(2S)-5,7,4′-trihydroxyflavanone 7-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the sakuranetin, an inducible defense mechanism of the plant Oryza sativa (Asian rice) against pathogen attack.
1.  Rakwal, R., Agrawal, G.K., Yonekura, M. and Kodama, O. Naringenin 7-O-methyltransferase involved in the biosynthesis of the flavanone phytoalexin sakuranetin from rice (Oryza sativa L.). Plant Sci. 155 (2000) 213–221. [PMID: 10814825]
[EC created 2011]
Accepted name: xanthohumol 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + xanthohumol = S-adenosyl-L-homocysteine + 4-O-methylxanthohumol
Glossary: xanthohumol = 2′,4,4′-trihydroxy-6′-methoxy-3-prenylchalcone = (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
4-O-methylxanthohumol =2′,4′-dihydroxy-4,6′-dimethoxy-3-prenylchalcone = (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-methoxyphenyl)prop-2-en-1-one
Other name(s): OMT2 (ambiguous); S-adenosyl-L-methionine:xanthohumol 4′-O-methyltransferase (incorrect); xanthohumol 4′-O-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:xanthohumol 4-O-methyltransferase
Comments: The enzyme from hops (Humulus lupulus) has a broad substrate specificity. The best substrates in vitro are resveratrol, desmethylxanthohumol, naringenin chalcone and isoliquiritigenin.
1.  Nagel, J., Culley, L.K., Lu, Y., Liu, E., Matthews, P.D., Stevens, J.F. and Page, J.E. EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol. Plant Cell 20 (2008) 186–200. [PMID: 18223037]
[EC created 2017, modified 2018]
Accepted name: chalcone synthase
Reaction: 3 malonyl-CoA + 4-coumaroyl-CoA = 4 CoA + naringenin chalcone + 3 CO2
Glossary: phloretin = 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one
Other name(s): naringenin-chalcone synthase; flavanone synthase; 6′-deoxychalcone synthase; chalcone synthetase; DOCS; CHS
Systematic name: malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing)
Comments: The enzyme catalyses the first committed step in the biosynthesis of flavonoids. It can also act on dihydro-4-coumaroyl-CoA, forming phloretin.
1.  Ayabe, S.-I., Udagawa, A. and Furuya, T. NAD(P)H-dependent 6′-deoxychalcone synthase activity in Glycyrrhiza echinata cells induced by yeast extract. Arch. Biochem. Biophys. 261 (1988) 458–462. [PMID: 3355160]
2.  Heller, W. and Hahlbrock, K. Highly purified "flavanone synthase" from parsley catalyzes the formation of naringenin chalcone. Arch. Biochem. Biophys. 200 (1980) 617–619. [PMID: 7436427]
3.  Yahyaa, M., Ali, S., Davidovich-Rikanati, R., Ibdah, M., Shachtier, A., Eyal, Y., Lewinsohn, E. and Ibdah, M. Characterization of three chalcone synthase-like genes from apple (Malus x domestica Borkh.). Phytochemistry 140 (2017) 125–133. [PMID: 28482241]
[EC created 1984, modified 2018]
Accepted name: trihydroxystilbene synthase
Reaction: 3 malonyl-CoA + 4-coumaroyl-CoA = 4 CoA + trans-resveratrol + 4 CO2
Glossary: trans-resveratrol = 3,4′,5-trihydroxy-trans-stilbene
Other name(s): resveratrol synthase; stilbene synthase (ambiguous)
Systematic name: malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing)
Comments: Not identical with EC naringenin-chalcone synthase or EC pinosylvin synthase.
1.  Schöppner, A. and Kindl, H. Purification and properties of a stilbene synthase from induced cell suspension cultures of peanut. J. Biol. Chem. 259 (1984) 6806–6811. [PMID: 6427224]
[EC created 1989]
Deleted entry:  6′-deoxychalcone synthase. The reaction listed is due to EC naringenin-chalcone synthase
[EC created 1990, deleted 1992]
Accepted name: pinosylvin synthase
Reaction: 3 malonyl-CoA + cinnamoyl-CoA = 4 CoA + pinosylvin + 4 CO2
Other name(s): stilbene synthase (ambiguous); pine stilbene synthase (ambiguous)
Systematic name: malonyl-CoA:cinnamoyl-CoA malonyltransferase (cyclizing)
Comments: Not identical with EC (naringenin-chalcone synthase) or EC (trihydroxystilbene synthase).
1.  Gehlert, R., Schöppner, A. and Kindl, H. Stilbene synthase from seedlings of Pinus sylvestris - purification and induction in response to fungal infection. Mol. Plant-Microbe Interaction 3 (1990) 444–449.
[EC created 1992]
Accepted name: phloroisovalerophenone synthase
Reaction: (1) isovaleryl-CoA + 3 malonyl-CoA = 4 CoA + 3 CO2 + phlorisovalerophenone
(2) isobutyryl-CoA + 3 malonyl-CoA = 4 CoA + 3 CO2 + phlorisobutyrophenone
Glossary: phlorisobutyrophenone = 2-methyl-1-(2,4,6-trihydroxyphenyl)propan-1-one
phlorisovalerophenone = 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one
Other name(s): valerophenone synthase; 3-methyl-1-(trihydroxyphenyl)butan-1-one synthase; acylphloroglucinol synthase; isovaleryl-CoA:malonyl-CoA acyltransferase
Systematic name: acyl-CoA:malonyl-CoA acyltransferase
Comments: Closely related to EC, naringenin-chalcone synthase. Also acts on isobutyryl-CoA as substrate to give phlorisobutyrophenone. The products are intermediates in the biosynthesis of the bitter acids in hops (Humulus lupulus) and glucosides in strawberry (Fragaria X ananassa). It is also able to generate naringenin chalcone from 4-coumaroyl-CoA.
1.  Fung, S.Y., Zuurbier, K.W.M., Paniego, N.B., Scheffer, J.J.C. and Verpoorte, R. Enzymes from the biosynthesis of hop α and β acids. Proc. 26th Congr. Eur. Brew. Conv. (1997) 215–221.
2.  Zuurbier, K.W.M., Leser, J., Berger, T., Hofte, A.J.P., Schroder, G., Verpoorte, R. and Schroder, J. 4-Hydroxy-2-pyrone formation by chalcone and stilbene synthase with nonphysiological substrates. Phytochemistry 49 (1998) 1945–1951. [PMID: 9883590]
3.  Song, C., Ring, L., Hoffmann, T., Huang, F.C., Slovin, J. and Schwab, W. Acylphloroglucinol biosynthesis in strawberry fruit. Plant Physiol. 169 (2015) 1656–1670. [PMID: 26169681]
[EC created 2000]
Accepted name: flavanone 7-O-β-glucosyltransferase
Reaction: UDP-glucose + a flavanone = UDP + a flavanone 7-O-β-D-glucoside
Other name(s): uridine diphosphoglucose-flavanone 7-O-glucosyltransferase; naringenin 7-O-glucosyltransferase; hesperetin 7-O-glucosyl-transferase
Systematic name: UDP-glucose:flavanone 7-O-β-D-glucosyltransferase
Comments: Naringenin and hesperetin can act as acceptors. No action on flavones or flavonols.
1.  McIntosh, C.A., Latchinian, L. and Mansell, R.L. Flavanone-specific 7-O-glucosyltransferase activity in Citrus paradisi seedlings: purification and characterization. Arch. Biochem. Biophys. 282 (1990) 50–57. [PMID: 2171434]
2.  McIntosh, C.A. and Mansell, R.L. Biosynthesis of naringin in Citrus paradisi - UDP-glucosyl-transferase activity in grapefruit seedlings. Phytochemistry 29 (1990) 1533–1538.
[EC created 1992]
Accepted name: flavanone 7-O-glucoside 2′′-O-β-L-rhamnosyltransferase
Reaction: UDP-β-L-rhamnose + a flavanone 7-O-β-D-glucoside = UDP + a flavanone 7-O-[α-L-rhamnosyl-(1→2)-β-D-glucoside]
Glossary: UDP-β-L-rhamnose = UDP-6-deoxy-β-L-mannose
Other name(s): UDP-rhamnose:flavanone-7-O-glucoside-2′′-O-rhamnosyltransferase; 1→2 UDP-rhamnosyltransferase; UDP-L-rhamnose:flavanone-7-O-glucoside 2′′-O-β-L-rhamnosyltransferase
Systematic name: UDP-β-L-rhamnose:flavanone-7-O-glucoside 2′′-O-α-L-rhamnosyltransferase
Comments: Acts on the 7-O-glucoside of naringenin and hesperetin, also the flavone 7-O-glucosides of luteolin and apigenin.
1.  Bar-Peled, M., Lewinsohn, E., Fluhr, R. and Gressel, J. UDP-rhamnose:flavanone-7-O-glucoside-2′′-O-rhamnosyltransferase. Purification and characterization of an enzyme catalyzing the production of bitter compounds in citrus. J. Biol. Chem. 266 (1991) 20953–20959. [PMID: 1939145]
[EC created 2004]
Accepted name: chalcone 4′-O-glucosyltransferase
Reaction: (1) UDP-α-D-glucose + naringenin chalcone = UDP + 2′,4,4′,6′-tetrahydroxychalcone 4′-O-β-D-glucoside
(2) UDP-α-D-glucose + 2′,3,4,4′,6′-pentahydroxychalcone = UDP + 2′,3,4,4′,6′-pentahydroxychalcone 4′-O-β-D-glucoside
Glossary: naringenin chalcone = 2′,4,4′,6′-tetrahydroxychalcone = 3-(4-hydroxyphemyl)-1-(2,4,6-trihydroxyphenyl)prop-2-en-1-one
Other name(s): 4′CGT
Systematic name: UDP-α-D-glucose:2′,4,4′,6′-tetrahydroxychalcone 4′-O-β-D-glucosyltransferase
Comments: Isolated from the plant Antirrhinum majus (snapdragon). Involved in the biosynthesis of aurones, plant flavonoids that provide yellow color to the flowers.
1.  Ono, E., Fukuchi-Mizutani, M., Nakamura, N., Fukui, Y., Yonekura-Sakakibara, K., Yamaguchi, M., Nakayama, T., Tanaka, T., Kusumi, T. and Tanaka, Y. Yellow flowers generated by expression of the aurone biosynthetic pathway. Proc. Natl. Acad. Sci. USA 103 (2006) 11075–11080. [PMID: 16832053]
[EC created 2012]
Accepted name: 2-hydroxyflavanone C-glucosyltransferase
Reaction: UDP-α-D-glucose + a 2′-hydroxy-β-oxodihydrochalcone = UDP + a 3′-(β-D-glucopyranosyl)-2′-hydroxy-β-oxodihydrochalcone
Glossary: 2′-hydroxy-β-oxodihydrochalcone = 1-(2-hydroxyphenyl)-3-phenypropan-1,3-dione
3′-(β-D-glucopyranosyl)-2′-hydroxy-β-oxodihydrochalcone = 1-(3-(β-D-glucopyranosyl)-2-hydroxyphenyl)-3-phenylpropan-1,3-dione
Other name(s): OsCGT
Systematic name: UDP-α-D-glucose:2′-hydroxy-β-oxodihydrochalcone C6/8-β-D-glucosyltransferase
Comments: The enzyme has been characterized in Oryza sativa (rice), various Citrus spp., Glycine max (soybean), and Fagopyrum esculentum (buckwheat). Flavanone substrates require a 2-hydroxy group. The meta-stable flavanone substrates such as 2-hydroxynaringenin exist in an equilibrium with open forms such as 1-(4-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propane-1,3-dione, which are the actual substrates for the glucosyl-transfer reaction (see EC, flavanone 2-hydroxylase). The enzyme can also act on dihydrochalcones. The enzymes from citrus plants can catalyse a second C-glycosylation reaction at position 5.
1.  Brazier-Hicks, M., Evans, K.M., Gershater, M.C., Puschmann, H., Steel, P.G. and Edwards, R. The C-glycosylation of flavonoids in cereals. J. Biol. Chem. 284 (2009) 17926–17934. [PMID: 19411659]
2.  Nagatomo, Y., Usui, S., Ito, T., Kato, A., Shimosaka, M. and Taguchi, G. Purification, molecular cloning and functional characterization of flavonoid C-glucosyltransferases from Fagopyrum esculentum M. (buckwheat) cotyledon. Plant J. 80 (2014) 437–448. [PMID: 25142187]
3.  Hirade, Y., Kotoku, N., Terasaka, K., Saijo-Hamano, Y., Fukumoto, A. and Mizukami, H. Identification and functional analysis of 2-hydroxyflavanone C-glucosyltransferase in soybean (Glycine max). FEBS Lett. 589 (2015) 1778–1786. [PMID: 25979175]
4.  Ito, T., Fujimoto, S., Suito, F., Shimosaka, M. and Taguchi, G. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants. Plant J. 91 (2017) 187–198. [PMID: 28370711]
[EC created 2018]
Accepted name: naringenin 8-dimethylallyltransferase
Reaction: prenyl diphosphate + (–)-(2S)-naringenin = diphosphate + sophoraflavanone B
Glossary: dimethylallyl = prenyl = 3-methylbut-2-en-1-yl
(–)-(2S)-naringenin = (–)-(2S)-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-dihydrochromen-4-one
Other name(s): N8DT; dimethylallyl-diphosphate:naringenin 8-dimethylallyltransferase
Systematic name: prenyl-diphosphate:naringenin 8-prenyltransferase
Comments: Requires Mg2+. This membrane-bound protein is located in the plastids [2]. In addition to naringenin, the enzyme can prenylate several other flavanones at the C-8 position, but more slowly. Along with EC (8-dimethylallylnaringenin 2′-hydroxylase) and EC (leachianone-G 2′′-dimethylallyltransferase), this enzyme forms part of the sophoraflavanone-G-biosynthesis pathway.
1.  Yamamoto, H., Senda, M. and Inoue, K. Flavanone 8-dimethylallyltransferase in Sophora flavescens cell suspension cultures. Phytochemistry 54 (2000) 649–655. [PMID: 10975499]
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. [PMID: 14551337]
[EC created 2007]
Accepted name: leachianone-G 2′′-dimethylallyltransferase
Reaction: prenyl diphosphate + leachianone G = diphosphate + sophoraflavanone G
Glossary: dimethylallyl = prenyl = 3-methylbut-2-en-1-yl
isopentenyl = 3-methylbut-3-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
sophoraflavanone G = (2S)-2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-8-[(2R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl]-2,3-dihydro-4H-chromen-4-one
Other name(s): LG 2′′-dimethylallyltransferase; leachianone G 2′′-dimethylallyltransferase; LGDT; dimethylallyl-diphosphate:leachianone-G 2′′-dimethylallyltransferase
Systematic name: prenyl-diphosphate:leachianone-G 2′′-prenyltransferase
Comments: This membrane-bound enzyme is located in the plastids and requires Mg2+ for activity. The reaction forms the lavandulyl sidechain of sophoraflavanone G by transferring a prenyl group to the 2′′ position of another prenyl group attached at position 8 of leachianone G. The enzyme is specific for prenyl diphosphate as the prenyl donor, as it cannot be replaced by isopentenyl diphosphate or geranyl diphosphate. Euchrenone a7 (a 5-deoxy derivative of leachianone G) and kenusanone I (a 7-methoxy derivative of leachianone G) can also act as substrates, but more slowly. Along with EC (8-dimethylallylnaringenin 2′-hydroxylase) and EC (naringenin 8-dimethylallyltransferase), this enzyme forms part of the sophoraflavanone-G-biosynthesis pathway.
1.  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. [PMID: 14551337]
[EC created 2007]
Accepted name: 2-acylphloroglucinol 4-prenyltransferase
Reaction: prenyl diphosphate + a 2-acylphloroglucinol = diphosphate + a 2-acyl-4-prenylphloroglucinol
Glossary: naringenin chalcone = 2′,4,4′,6′-tetrahydroxychalcone = 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)prop-2-en-1-one
phlorisovalerophenone = 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one
Other name(s): PT-1 (gene name); PT1L (gene name); aromatic prenyltransferase (ambiguous); dimethylallyl-diphosphate:2-acylphloroglucinol 4-dimethylallyltransferase
Systematic name: prenyl-diphosphate:2-acylphloroglucinol 4-prenyltransferase
Comments: The enzyme, characterized from hop (Humulus lupulus), acts on phlorisovalerophenone, phlormethylbutanophenone, and phlorisobutanophenone during the synthesis of bitter acids. It also acts with much lower activity on naringenin chalcone. Forms a complex with EC, 2-acyl-4-prenylphloroglucinol 6-prenyltransferase, which catalyses additional prenylation reactions. Requires Mg2+.
1.  Tsurumaru, Y., Sasaki, K., Miyawaki, T., Uto, Y., Momma, T., Umemoto, N., Momose, M. and Yazaki, K. HlPT-1, a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops. Biochem. Biophys. Res. Commun. 417 (2012) 393–398. [PMID: 22166201]
2.  Li, H., Ban, Z., Qin, H., Ma, L., King, A.J. and Wang, G. A heteromeric membrane-bound prenyltransferase complex from hop catalyzes three sequential aromatic prenylations in the bitter acid pathway. Plant Physiol. 167 (2015) 650–659. [PMID: 25564559]
[EC created 2017]