This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis → Phenylpropanoid Derivatives Biosynthesis → Flavonoids Biosynthesis → Flavonols Biosynthesis|
Expected Taxonomic Range: Spermatophyta
The 3',5'-methylated flavonol syringetin and its precursor myricetin has been found throughout the plant kingdom (e.g. [Mizuno92] [Kaundun00] [Wang03a] [Hibasami05] but as for many other flavonoids the glycosylated derivatives occur more frequently than their aglycons [Wollenweber94] [Williams94a].
The occurrence of laricitrin, the 3'-monomethylated derivative of myricetin and direct precursor for syringetin has been verified during metabolic profiling in plants [Mattivi06]. That demonstrates the existence of that compound (and its glucosides) on its own, indicating that laricitrin is not merely a transient intermediate of the pathway as assumed earlier. The pharmaceutical importance for human health has been demonstrated for many flavonols (for example pinobanksin biosynthesis, kaempferol glycoside biosynthesis (Arabidopsis), rutin biosynthesis). Similar reports exist with regard to myricetin and its methylated derivatives. The therapeutic potential of these compounds are considerable, as antioxidants as well as their use as anti-inflammatory, antiartherosclerotic and antithrombotic agents that have been revealed in related animal research (reviewed by [Ong97]). Moreover, myricetin was found to reduce the danger of skin cancer, indicating its usefulness as an anticarcinogen [Mukhtar88].
About This Pathway
The enzymatic step(s) representing the entry towards the biosynthetic route of syringetin are catalyzed by enzymes that form the intermediate dihydromyricetin. That is the first flavonol bearing three hydroxyl groups on the flavonoid B-ring. Dihydromyricetin is the branch point flavonol that is central to both the formation of syringetin and the biosynthesis of corresponding anthocyanins such as delphinidin (see anthocyanin biosynthesis (delphinidin 3-O-glucoside)) and derivatives thereof (e.g. petunidin, hirsutin, ternatin). The enzymes catalyzing the formation of dihydromyrecetin are cytochrome P450 dependent monooxygenases that either introduce two hydroxyl groups to dihydrokaempferol (flavonoid 3',5'-hydroxylases)(e.g. [Kaltenbach99]) or form that compound using the successive interconnection of flavonoid 3'-hydroxylase (e.g. [Brugliera99]) and flavonoid 3',5'-hydroxylase (e.g. [Shimada99]) via dihydroquercetin.
The 2-oxoglutarate dependent flavonol synthase catalyzing the formation of flavonols from dihydroflavonols (EC 184.108.40.206) have been found in several plants [Fujita06] [Lukacin03] [Martens03] however the specific conversion of dihyromyricetin to myricetin remains to be corroborated.
The final step in the pathway, the 3'- and 5'-O-methylation forming laricitrin and syringetin, respectively is carried out by a unique O-methyltransferase (CrOMT2) that catalyzes two consecutive methylation steps on the same substrate. It was demonstrated that dihydromyricetin was also a suitable substrate for this enzyme. The methylation pattern corresponds to the glycosides and anthocyanins found in Catharanthus roseus which supports the involvement of CrOMT2 in their biosynthesis [Cacace03].
Superpathways: superpathway of flavones and derivatives biosynthesis
Brugliera99: Brugliera F, Barri-Rewell G, Holton TA, Mason JG (1999). "Isolation and characterization of a flavonoid 3'-hydroxylase cDNA clone corresponding to the Ht1 locus of Petunia hybrida." Plant J 19(4);441-51. PMID: 10504566
Cacace03: Cacace S, Schroder G, Wehinger E, Strack D, Schmidt J, Schroder J (2003). "A flavonol O-methyltransferase from Catharanthus roseus performing two sequential methylations." Phytochemistry 62(2);127-37. PMID: 12482447
Fujita06: Fujita A, Goto-Yamamoto N, Aramaki I, Hashizume K (2006). "Organ-specific transcription of putative flavonol synthase genes of grapevine and effects of plant hormones and shading on flavonol biosynthesis in grape berry skins." Biosci Biotechnol Biochem 70(3);632-8. PMID: 16556978
Hibasami05: Hibasami H, Mitani A, Katsuzaki H, Imai K, Yoshioka K, Komiya T (2005). "Isolation of five types of flavonol from seabuckthorn (Hippophae rhamnoides) and induction of apoptosis by some of the flavonols in human promyelotic leukemia HL-60 cells." Int J Mol Med 15(5);805-9. PMID: 15806302
Kaltenbach99: Kaltenbach M, Schroder G, Schmelzer E, Lutz V, Schroder J (1999). "Flavonoid hydroxylase from Catharanthus roseus: cDNA, heterologous expression, enzyme properties and cell-type specific expression in plants." Plant J 19(2);183-93. PMID: 10476065
Kaundun00: Kaundun SS, Lebreton P, Bailly A (2000). "Discrimination and identification of coastal Douglas-fir clones using needle flavonoid fingerprints." Biochem Syst Ecol 28(8);779-791. PMID: 10856635
Martens03: Martens S, Forkmann G, Britsch L, Wellmann F, Matern U, Lukacin R (2003). "Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley." FEBS Lett 544(1-3);93-8. PMID: 12782296
Mukhtar88: Mukhtar H, Das M, Khan WA, Wang ZY, Bik DP, Bickers DR (1988). "Exceptional activity of tannic acid among naturally occurring plant phenols in protecting against 7,12-dimethylbenz(a)anthracene-, benzo(a)pyrene-, 3-methylcholanthrene-, and N-methyl-N-nitrosourea-induced skin tumorigenesis in mice." Cancer Res 48(9);2361-5. PMID: 3128399
Shimada99: Shimada Y, Nakano-Shimada R, Ohbayashi M, Okinaka Y, Kiyokawa S, Kikuchi Y (1999). "Expression of chimeric P450 genes encoding flavonoid-3', 5'-hydroxylase in transgenic tobacco and petunia plants(1)." FEBS Lett 461(3);241-5. PMID: 10567704
Ibdah03: Ibdah M, Zhang XH, Schmidt J, Vogt T (2003). "A novel Mg(2+)-dependent O-methyltransferase in the phenylpropanoid metabolism of Mesembryanthemum crystallinum." J Biol Chem 278(45);43961-72. PMID: 12941960
Kopycki08: Kopycki JG, Rauh D, Chumanevich AA, Neumann P, Vogt T, Stubbs MT (2008). "Biochemical and structural analysis of substrate promiscuity in plant Mg2+-dependent O-methyltransferases." J Mol Biol 378(1);154-64. PMID: 18342334
Schmidt11: Schmidt A, Li C, Shi F, Jones AD, Pichersky E (2011). "Polymethylated myricetin in trichomes of the wild tomato species Solanum habrochaites and characterization of trichome-specific 3'/5'- and 7/4'-myricetin O-methyltransferases." Plant Physiol 155(4);1999-2009. PMID: 21343428
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