MetaCyc Pathway: syringetin biosynthesis
Traceable author statement to experimental supportInferred from experiment

Enzyme View:

Pathway diagram: syringetin biosynthesis

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: BiosynthesisSecondary Metabolites BiosynthesisPhenylpropanoid Derivatives BiosynthesisFlavonoids BiosynthesisFlavonols Biosynthesis

Some taxa known to possess this pathway include : Catharanthus roseus, Eustoma exaltatum russellianum, Petunia x hybrida

Expected Taxonomic Range: Spermatophyta

General Background

The 3',5'-methylated flavonol syringetin and its precursor myricetin has been found throughout the plant kingdom (e.g. [Mizuno92] [Kaundun00] [Wang03c] [Hibasami05] but as for many other flavonoids the glycosylated derivatives occur more frequently than their aglycons [Wollenweber94] [Williams94].

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 have been found in several plants [Fujita06a] [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

Created 03-Nov-2006 by Foerster H, TAIR


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

Fujita06a: 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

Lukacin03: Lukacin R, Wellmann F, Britsch L, Martens S, Matern U (2003). "Flavonol synthase from Citrus unshiu is a bifunctional dioxygenase." Phytochemistry 62(3);287-92. PMID: 12620339

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

Mattivi06: Mattivi F, Guzzon R, Vrhovsek U, Stefanini M, Velasco R (2006). "Metabolite profiling of grape: Flavonols and anthocyanins." J Agric Food Chem 54(20);7692-702. PMID: 17002441

Mizuno92: Mizuno M, Yoshida S, Iinuma M, Tanaka T, Tsuji K, Lang FA (1992). "Four flavonol glycosides from Achlys triphylla." Phytochemistry 31(1);301-3. PMID: 1367884

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

Ong97: Ong KC, Khoo HE (1997). "Biological effects of myricetin." Gen Pharmacol 29(2);121-6. PMID: 9251891

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

Wang03c: Wang H, Race EJ, Shrikhande AJ (2003). "Anthocyanin transformation in Cabernet Sauvignon wine during aging." J Agric Food Chem 51(27);7989-94. PMID: 14690384

Williams94: Williams CA, Harborne JB (1994). "Flavone and flavonol glycosides." In: Harborne JB (editor) The flavonoids: Advances in research since 1986; Chapman and Hall, London, 337-385.

Wollenweber94: Wollenweber E (1994). "Flavones and Flavonols." In: Harborne JB (editor) The flavonoids: Advances in research since 1986; Chapman and Hall, London, 259-336.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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