Biosynthesis of flavonols

Jourdan PS, Mansell RL (1982) Isolation and partial characterization of three glucosyl transferases involved in the biosynthesis of flavonol tiiglucosides in Pisum sativum L. Arch Biochem Biophys 213 434-443... 

Fig. 7 Biosynthesis of flavonols (35) via naringenin (1) from tetrahydroxychalcone (chalcone, 18)...

Certain dihydroflavonols are intermediates in the biosynthesis of flavonols, but approximately 110 other dihydroflavonols and dihydroflavonol glycosides are found in a variety of families, especially the Asteraceae and Fabaceae (Grayer, 1989). 

Many steps of proanthocyanidin biosynthesis have recently been reviewed [59]. The genes encoding the key enzymes of biosynthesis of flavonols, the transport... 

Figure 5.4. Abbreviated scheme for biosynthesis of major flavonoid subclasses, showing the primary enzymes and substrates leading to different subclasses. Bold-faced, uppercase abbreviations refer to enzyme names, whereas substrate names are presented in lowercase letters. PAL, phenylalanine ammonia lyase C4H, cinnamate 4-hydroxylase 4CL, 4-coumarate CoA ligase CHS, chalcone synthase CHI, chalcone isomerase CHR, chalcone reductase IPS, isoflavone synthase F3H, flavonone 3-hydroxylase F3 H, flavonoid 3 -hydroxylase F3 5 H, flavonoid 3 5 -hydroxylase FNSI/II, flavone synthase DFR, dihydroflavonol 4-reductase FLS, flavonol synthase ANS, anthocyanidin synthase LAR, leucoanthocyanidin reductase ANR, anthocyanidin reductase UFGT, UDP-glucose flavonoid 3-O-glucosyltransferase. R3 = H or OH. R5 = H or OH. Glc = glucose. Please refer to text for more information.

Stitch K, Eidenberger T, Wurst F, Forkmann G (1992) Flavonol synthase activity and the regulation of flavonol and anthocyanin biosynthesis during flower development in Dianthus caryophyllus. Z Naturforsch 47C 553-560... 

Regulation of Flavonoid Synthesis in C. americanum. Biosynthesis of methylated flavonol glucosides seems to be under tight regulation, not only by the substrate specificity of the enzymes involved, but also by other factors, among which are (a) the strict position specificity of these enzymes towards their hydroxylated or partially methylated substrates (b) the apparent difference in microenvironment of the different methyl-transferases, whereby those earlier in the pathway utilized aglycones whereas later enzymes accepted only glucosides as substrates (c) the subtle characteristic differences in methyl-transferases with respect to their pH optima, pi values and requirement for Mg ions, despite their similar molecular size ... 

Biogenetically, chalcones are the immediate precursors of flavanones, and some flavanones isomerize by ring opening into chalcones during isolation from plants or after chemical treatment with alkali. In turn, flavanones are intermediates in the biosynthesis of most other flavonoid groups, including flavones, flavonols, and isoflavonoids. For more information on the biosynthesis of flavonoids and flavanones in particular, the reader is referred to Chapter 3 and reviews by Heller and Forkmann. ... 

Proanthocyanidins and Procyanidins - In a classical study Bate-Smith ( ) used the patterns of distribution of the three principal classes of phenolic metabolites, which are found in the leaves of plants, as a basis for classification. The biosynthesis of these phenols - (i) proanthocyanidins (ii) glycosylated flavonols and (iii) hydroxycinnamoyl esters - is believed to be associated with the development in plants of the capacity to synthesise the structural polymer lignin by the diversion from protein synthesis of the amino-acids L-phenylalanine and L-tyro-sine. Vascular plants thus employ one or more of the p-hydroxy-cinnarayl alcohols (2,3, and 4), which are derived by enzymic reduction (NADH) of the coenzyme A esters of the corresponding hydroxycinnamic acids, as precursors to lignin. The same coenzyme A esters also form the points of biosynthetic departure for the three groups of phenolic metabolites (i, ii, iii), Figure 1. 

Similarly to L. densiflora, L. heteromorpha is unusual for its biosynthesis of methoxylated flavonoids glycosides (with the methoxyl groups at C-4 of ring B and C-7 of ring A). The production of such flavonoids could be a response to local environmental factors. In comparison to the other Licania species, L. heteromorpha predominantly yields flavonol glycosides instead of flavones or flavanones. 

Leonard E, Yan Y, Koffas MA. 2006b. Functional expression of a P450 flavonoid hydroxylase for the biosynthesis of plant-specific hydroxylated flavonols in Escherichia coli. Metab Eng 8 172-181. 

Scheme 1.1 Pathway for the biosynthesis of the major classes of flavonoids. 1, Chalcone synthase 2, chalcone isomerase 3, flavone synthase 4, flavanone 3-hydroxylase 5, flavonol synthase 6, dihydroflavonol reductase 7, anthocyanidin synthase 8, anthocyanidin glucosyltransferase 9, chalcone-ketide reductase 10, chalcone isomerase 11, isoflavone synthase 12, isoflavone 2 -hydroxylase 13, isoflavone reductase 14, pterocarpan synthase 15, pterocarpan 6a-hydroxylase 16, prenyltransferase 17, prenylcyclase.

Miyahisa, L, Funa, N., Ohnishi, Y., Martens, S., Moriguchi, T. and Horinouchi, S. (2006) Combinatorial biosynthesis of flavones and flavonols in Escherichia coli. Appl. Biotechnol. Microbiol, 71, 53-8. 

Production of flavonols begins before the veraison in the first period of veraison quercetin is the main flavonol present (the dihydroquercetin biosynthesis prevails) and production of myricetin is slower but, in varieties where biosynthesis of dihydromyricetin prevails, myricetin can be the main flavonol (Borsa, personal communication Squadrito etal., 2006). 

Fig, 5.2. Biosynthesis of flavonoids and proanthocyanidins (condensed tannins). Enzymes in bold have been cloned from P. tremuloides and show induction by herbivory (Peters and Constabel, 2002 R. Mellway and C. P. Constabel, unpublished data). Abbreviations are as follows Phe, phenylalanine PAL, phenylalanine ammonia lyase 4CL, 4-coumarate CoA Ligase CHS, chalcone synthase CHI, chalcone isomerase F3H, flavanone 3-hydroxylase FLS, flavonol synthase DFR,... 

FIGURE 10.5 Biosynthesis of phenolic acids. (Adapted from Duthie, G. and Crozier, A., Curr. Opin. Lipid, 11,43, 2000 Hakkinen, S., Flavonols and phenolic acids in berries and berry products. Doctoral dissertation, Kuopio University Publications, Kuopio, Finland, D. Med. ScL, 221, 92, 2000.)... 

Biosynthesis of Flavonoids Initial Steps of Flavonoid Biosynthesis Chalcones as Intermediates in Flavonoid Biosynthesis Flavanones Flavones Dihydroflavonols Flavonols... 

Biosynthesis of C-Glycosyl Flavonoids Biosynthesis of Anthocyanins Systematic Studies with Flavone and Flavonol Glycosides Biological Activity of Flavone and Flavonol Aglycones and Glycosides... 

Many aspects of the biosynthesis of flavonoids have been elucidated, but major progress in sorting out certain reaction steps and the enzymes involved in flavonoid biosynthesis was not possible before tissue and cell culture of suitable plants were developed (Hutchinson, 1986). The use of flowers as sources of enzymes has provided the means for producing " C-labeled substrates (Heller and Forkmann, 1988). Cell cultures of Petroselinum hortense (parsley, Apiaceae) contain both flavone and flavonol glycosides most of the approximately 13 enzymes that catalyze the formation of flavonoid glycosides have been isolated and studied. Light... 

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