Flavonoid Biosynthesis – https://www.kegg.jp/kegg-bin/highlight_pathway?scale=1.0&map=map00941&keyword=flavonoids Flavonoids are a major class of plant secondary metabolites that serves a multitude of functions including pigments and antioxidant activity. Flavonoids are synthesized from phenylpropanoid derivatives by condensation with malonyl- CoA. For example, condensation of p-coumaroyl-CoA (C6-C3) with three malonyl-CoA (C3) molecules results in naringenin chalcone with a diphenylpropane (C6-C3-C6) unit, which is converted to naringenin with the flavone (2-phenylchromen-4-one) backbone by conjugate ring closure. These and further modifications yield a variety of structural forms including chalcones, flavanones, dihyroflavonols, and flavans, anthocyanins, flavones and flavonols, and isoflavonoids. (Phenylpropanoid Biosynthesis) -> [1,2] 1) Cinnamoyl-CoA -> [1,2] 1) chalcone synthase -> Pinocembrin chalcone -> chalcone isomerase -> Pinocembrin -> [1,2,3] 1) Pinostrobin OR 2) flavone synthase I -> Chrysin OR 3) naringenin 3- dioxygenase -> Pinobanksin -> [1,2] 1) flavonol synthase -> Galangin OR 2) Pinobanksin 3-O- acetate OR 2) trans-cinnamate 4-monooxygenase -> p-Coumaroyl-CoA -> [1,2,3,4,5,6] 1) chalcone synthase -> isoliquiritigenin -> [1,2] 1) Butein -> chalcone isomerase -> Butin -> naringenin 3-dioxygenase -> Fustin -> bifunctional dihydroflavonol 4-reductase/flavanone 4- reductase <-> Fisetinidol-4beta-ol <-> Fustin OR 2) chalcone isomerase -> Liquiritgenin [1,2,3,4] 1) flavonoid 3’-monooxygenase -> Butin -> naringenin 3-dioxygenase -> Fustin -> bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase <-> Fisetinidol-4beta-ol <-> Fustin OR 2) flavone synthase I & II -> 7,4’-dihydroxyflavone OR 3) (Isoflavonoid Biosynthesis) OR 4) naringenin 3-dioxygenase -> Garbanzol -> [1,2] 1) bifunctional dihydroflavonol 4- reductase/flavanone 4-reductase -> 5-deoxyleucopelargonidin <-> garbanzol OR 2) flavonoid 3’- monooxygenase -> Fustin -> bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase <- > Fisetinidol-4beta-ol <-> Fustin OR 2) hydroxycinnamoyl-CoA reductase -> Dihydro-4- coumaroyl-CoA -> chalcone synthase -> Phloretin -> phlorizin synthase -> Phlorizin OR 3) chalcone synthase -> Naringenin chalcone -> [1,2,3,4] 1) chalcononaringenin 2’-O- glucosyltransferase -> Chalcone 2’-O-glucoside OR 2) chalcone 4’-O-glucosyltransferase -> 2’,4,4’,6’-Tetrahydroxychalcone 4’-O-glucoside -> aureusidin synthase -> Aureusidin 6-O- glucoside OR 3) desmethylxanthohumol -> desmethylxanthohumol 6’-O-methyltransferase -> xanthohumol 4’-O-methyltransferase -> 4-O-Methylxanthohumol OR 4) chalcone isomerase -> naringenin -> [1…10] 1) (Isoflavonoid Biosynthesis) OR 2) flavanone 7-O-beta-glucosyltransferase -> Prunin -> flavanone 7-O-glucoside 2’’-O-beta-L-rhamnosyltransferase -> Naringin OR 3) Hesperetin -> flavanone 7-O-beta-glucosyltransferase -> Hesperetin 7-O-glucoside -> flavanone 7-O-glucoside 2’’-O-beta-L-rhamnosyltransferase -> Neohesperidin OR 4) flavonoid 4’-O- methyltransferase -> Isosakuranetin OR 5) naringenin 3-dioxygenase -> Dihydrokaempferol -> [1,2,3] 1) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> cis-3,4- Leucopelargonidin -> [1,2,3] 1) anthocyanidin synthase -> Dihydrokaempferol (Feedback Loop) OR 2) leucoanthocyanidin reductase -> Afzelechin OR 3) anthocyanidin synthase -> Pelargonidin -> [1,2] 1) anthocyanidin reductase -> (-)-epiafzelechin OR 2) (Anthocyanin Biosynthesis) OR 2) flavonol synthase -> Kaempferol -> [1,2] 1) (flavone and flavonol biosynthesis) OR 2) flavonoid 3’,5’-hydroxylase & flavonoid 3’-monooxygenase -> Quercetin -> flavonoid 3’,5’hydroxylase -> Hansford Boutchyard IV www.phytpharma.com 2/24/21 Myricetin OR 3) flavonoid 3’,5’-hydroxylase & flavonoid 3’-monooxygenase -> Dihydroquercetin -> bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucocyanidin -> [1,2,3] 1) anthocyanidin synthase -> Dihydroquercetin (Feedback Loop) OR 2) leucoanthocyanidin reductase -> (+)-Catechin OR 3) anthocyanidin synthase -> Cyanidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epicatechin OR 3) flavonoid 3’,5’-hydroxylase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 6) naringenin 7-O-methyltransferase -> Sakuranetin OR 7) bifunctional dihydroflavonol 4- reductase/flavanone 4-reductase -> Apiforol OR 8) 8-C-Glucosylnaringenin -> Vitexin OR 9) flavone synthase I & II -> Apigenin -> [1,2,3] 1) Vitexin OR 2) (Flavone and Flavonol Biosynthesis) OR 3) flavonoid 3’,5’-hydroxylase & flavonoid 3’-monooxygenase -> Luteolin -> flavonoid 3’,5’- hydroxylase -> Tricetin -> flavone synthase I -> Dihydrotricetin -> naringenin 3-dioxygenase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 10) flavonoid 3’,5’- hydroxylase & flavonoid 3’-monooxygenase -> Eriodictyol -> [1,2,3,4,5] 1) naringenin 3- dioxygenase -> dihydroquercetin -> Dihydroquercetin -> bifunctional dihydroflavonol 4- reductase/flavanone 4-reductase -> Leucocyanidin -> [1,2,3] 1) anthocyanidin synthase -> Dihydroquercetin (Feedback Loop) OR 2) leucoanthocyanidin reductase -> (+)-Catechin OR 3) anthocyanidin synthase -> Cyanidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epicatechin OR 3) flavonoid 3’,5’-hydroxylase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4- reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 2) flavone synthase I & II -> Luteolin -> flavonoid 3’,5’-hydroxylase -> Tricetin -> flavone synthase I -> Dihydrotricetin -> naringenin 3- dioxygenase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 3) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Luteoforol OR 4) flavonoid 3’,5’-hydroxylase -> Dihydrotricetin -> naringenin 3-dioxygenase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4- reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 5) homoeriodictyol OR 4) shikimate O- hydroxycinnamoyltransferase -> p-Coumaroyl quinic acid -> 5-O-(4-coumaroyl)-D-quinate 3’- monooxygenase -> Caffeoyl quinic acid -> shikimate O-hydroxycinnamoyltransferase -> Caffeoyl- CoA -> [1,2] 1) caffeoyl-CoA O-methyltransferase -> Feruloyl-CoA -> chalcone synthase -> homoeriodictyol chalcone -> homoeriodictyol OR 2) chalcone synthase -> Eriodictyol chalcone -> [1,2,3] 1) homoeriodictyol chalcone -> homoeriodictyol OR 2) Eriodictyol -> [1,2,3,4,5] 1) Hansford Boutchyard IV www.phytpharma.com 2/24/21 naringenin 3-dioxygenase -> dihydroquercetin -> Dihydroquercetin -> bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucocyanidin -> [1,2,3] 1) anthocyanidin synthase -> Dihydroquercetin (Feedback Loop) OR 2) leucoanthocyanidin reductase -> (+)- Catechin OR 3) anthocyanidin synthase -> Cyanidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epicatechin OR 3) flavonoid 3’,5’-hydroxylase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4- reductase/flavanone 4-reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase - > (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 2) flavone synthase I & II - > Luteolin -> flavonoid 3’,5’-hydroxylase -> Tricetin -> flavone synthase I -> Dihydrotricetin -> naringenin 3-dioxygenase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin OR 3) bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase -> Luteoforol OR 4) flavonoid 3’,5’-hydroxylase -> Dihydrotricetin -> naringenin 3-dioxygenase -> Dihydromyricetin -> [1,2] 1) flavonol synthase -> Myricetin OR 2) bifunctional dihydroflavonol 4-reductase/flavanone 4- reductase -> Leucodelphinidin -> [1,2] 1) leucoanthocyanidin reductase -> (+)-Gallcatechin OR 2) anthocyanidin synthase -> Delphinidin -> [1,2] 1) (Anthocyanin Biosynthesis) OR 2) anthocyanidin reductase -> (-)-Epigallocatechin