Accepted name: dihydroflavonol 4-reductase
Reaction: a (2R,3S,4S)-leucoanthocyanidin + NADP+ = a (2R,3R)-dihydroflavonol + NADPH + H+
Other name(s): dihydrokaempferol 4-reductase; dihydromyricetin reductase; NADPH-dihydromyricetin reductase; dihydroquercetin reductase; DFR (gene name); cis-3,4-leucopelargonidin:NADP+ 4-oxidoreductase; dihydroflavanol 4-reductase (incorrect)
Systematic name: (2R,3S,4S)-leucoanthocyanidin:NADP+ 4-oxidoreductase
Comments: This plant enzyme, involved in the biosynthesis of anthocyanidins, is known to act on (+)-dihydrokaempferol, (+)-taxifolin, and (+)-dihydromyricetin, although some enzymes may act only on a subset of these compounds. Each dihydroflavonol is reduced to the corresponding cis-flavan-3,4-diol. NAD+ can act instead of NADP+, but more slowly.
1.  Heller, W., Forkmann, G., Britsch, L. and Grisebach, H. Enzymatic reduction of (+)-dihydroflavonols to flavan-3,4-cis- diols with flower extracts from Matthiola incana and its role in anthocyanin biosynthesis. Planta 165 (1985) 284–287. [PMID: 24241054]
2.  Stafford, H.A. and Lester, H.H. Flavan-3-ol biosynthesis the conversion of (+)-dihydromyricetin to its flavan-3,4-diol (leucodelphinidin) and to (+)-gallocatechin by reductases extracted from tissue-cultures of Ginkgo biloba and Pseudotsuga-menziesii. Plant Physiol. 78 (1985) 791–794. [PMID: 16664326]
3.  Fischer, D., Stich, K., Britsch, L. and Grisebach, H. Purification and characterization of (+)dihydroflavonol (3-hydroxyflavanone) 4-reductase from flowers of Dahlia variabilis. Arch. Biochem. Biophys. 264 (1988) 40–47. [PMID: 3293532]
4.  Li, H., Qiu, J., Chen, F., Lv, X., Fu, C., Zhao, D., Hua, X. and Zhao, Q. Molecular characterization and expression analysis of dihydroflavonol 4-reductase (DFR) gene in Saussurea medusa. Mol. Biol. Rep. 39 (2012) 2991–2999. [PMID: 21701830]
[EC created 1989, modified 2016]
Transferred entry: flavonol synthase. Now EC, flavonol synthase
[EC created 2004, deleted 2018]
Transferred entry: flavanoid 3,5-hydroxylase. Now EC, flavanoid 3,5-hydroxylase
[EC created 2004, 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: 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]
Deleted entry: myricetin O-methyltransferase. Now covered by EC, flavonoid 3′,5′-methyltransferase.
[EC created 2003, modified 2011, deleted 2013]
Accepted name: flavonoid 3′,5′-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + a 3′-hydroxyflavonoid = S-adenosyl-L-homocysteine + a 3′-methoxyflavonoid
(2) S-adenosyl-L-methionine + a 5′-hydroxy-3′-methoxyflavonoid = S-adenosyl-L-homocysteine + a 3′,5′-dimethoxyflavonoid
Glossary: delphinidin = 3,3′,4′,5,5′,7-hexahydroxyflavylium
cyanidin = 3,3′,4′,5,7-pentahydroxyflavylium
myricetin = 3,3′,4′,5,5′,7-hexahydroxyflavone
quercetin = 3,3′,4′,5,7-pentahydroxyflavone
Other name(s): AOMT; CrOMT2
Systematic name: S-adenosyl-L-methionine:flavonoid 3′-O-methyltransferase
Comments: Isolated from Vitis vinifera (grape) [2]. Most active with delphinidin 3-glucoside but also acts on cyanidin 3-glucoside, cyanidin, myricetin, quercetin and quercetin 3-glucoside. The enzyme from Catharanthus roseus was most active with myricetin [1].
1.  Cacace, S., Schröder, G., Wehinger, E., Strack, D., Schmidt, J. and Schröder, J. A flavonol O-methyltransferase from Catharanthus roseus performing two sequential methylations. Phytochemistry 62 (2003) 127–137. [PMID: 12482447]
2.  Hugueney, P., Provenzano, S., Verries, C., Ferrandino, A., Meudec, E., Batelli, G., Merdinoglu, D., Cheynier, V., Schubert, A. and Ageorges, A. A novel cation-dependent O-methyltransferase involved in anthocyanin methylation in grapevine. Plant Physiol. 150 (2009) 2057–2070. [PMID: 19525322]
[EC created 2013, modified 2014]
Accepted name: kaempferol 3-O-galactosyltransferase
Reaction: UDP-α-D-galactose + kaempferol = UDP + kaempferol 3-O-β-D-galactoside
Other name(s): F3GalTase; UDP-galactose:kaempferol 3-O-β-D-galactosyltransferase
Systematic name: UDP-α-D-galactose:kaempferol 3-O-β-D-galactosyltransferase
Comments: Acts on the endogenous flavonols kaempferol and quercetin, to a lesser extent on myricetin and fisetin, and weakly on galangin and isorhamnetin. The reaction can occur equally well in both directions.
1.  Miller, K.D., Guyon, V., Evans, J.N., Shuttleworth, W.A. and Taylor, L.P. Purification, cloning, and heterologous expression of a catalytically efficient flavonol 3-O-galactosyltransferase expressed in the male gametophyte of Petunia hybrida. J. Biol. Chem. 274 (1999) 34011–34019. [PMID: 10567367]
[EC created 2004]
Accepted name: flavonol 7-O-β-glucosyltransferase
Reaction: UDP-glucose + a flavonol = UDP + a flavonol 7-O-β-D-glucoside
Other name(s): UDP-glucose:flavonol 7-O-glucosyltransferase
Systematic name: UDP-glucose:flavonol 7-O-β-D-glucosyltransferase
Comments: Acts on the flavonols gossypetin (8-hydroxyquercetin) and to a lesser extent on quercetin, kaempferol and myricetin.
1.  Stich, K., Halbwirth, H., Wurst, F. and Forkmann, G. UDP-glucose: flavonol 7-O-glucosyltransferase activity in flower extracts of Chrysanthemum segetum. Z. Naturforsch. C 52 (1997) 153–158. [PMID: 9167271]
[EC created 2004]
Accepted name: kaempferol 3-O-xylosyltransferase
Reaction: UDP-α-D-xylose + kaempferol = UDP + kaempferol 3-O-β-D-xyloside
Other name(s): F3XT; UDP-D-xylose:flavonol 3-O-xylosyltransferase; flavonol 3-O-xylosyltransferase
Systematic name: UDP-α-D-xylose:kaempferol 3-O-D-xylosyltransferase
Comments: The enzyme from the plant Euonymus alatus also catalyses the 3-O-D-xylosylation of other flavonols (e.g. quercetin, isorhamnetin, rhamnetin, myricetin, fisetin) with lower activity.
1.  Ishikura, N. and Yang, Z.Q. UDP-D-xylose: flavonol 3-O-xylosyltransferase from young leaves of Euonymus alatus f. ciliato-dentatus. Z. Naturforsch. C: Biosci. 46 (1991) 1003–1010.
[EC created 2013]