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MetaCyc Pathway: hispidol and hispidol 4'-O-β-D-glucoside biosynthesis

Pathway diagram: hispidol and hispidol 4'-O-beta-D-glucoside biosynthesis

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 Aurones Biosynthesis

Some taxa known to possess this pathway include ? : Medicago truncatula

Expected Taxonomic Range: Fabaceae

Summary:
Aurones are a subclass of flavonoids derived from the phenylpropanoid biosynthesis pathway. In legumes the chalcone synthase forms 6-deoxy isoliquiritigenin as a diverging set of secondary metabolites. The molecule isoliquiritigenin is metabolized to (2S)-liquiritigenin via chalcone isomerase, a precursor molecule to a range of 5 deoxy flavone, flavonols and isoflavone. However, the route for aurone biosynthesis deviates from these other products as they are directly synthesized from isoliquiritigenin [Farag09]. Aurones are implicated in flower pigmentation [Nakayama00], [Nakayama01], and in defense responses. For humans they are important as anticancer, anti-diabetic and antibacterial agents.

Hispidol was isolated from Soya hispida along with isoflavone and isoflavone glucosides [Frakas68]. Hispidol and its glucosides are elicited in response to yeast elicitor or methyl jasmonate (MeJa) treatments. Their role in plant defense and as antifungal agents has been demonstrated. Hispidol has been hypothesized as being formed as a result of spillover of precursor molecule isoliquiritigenin from the phenylpropanoid biosynthesis, thus balancing the upstream and downstream activities of the phenylpropanoid biosynthesis [Farag09]. The peroxidase enzymes are implicated as the catalyzing agents for hispidol. However, the presence and accumulation of these enzymes in the roots where hispidol does not accumulate may indicate that the formation of hispidol may be only one of the functions of these enzymes [Farag09].

The pathway depicted above is based on experimental findings with three peroxidases in Medicago truncatula, i.e. PRX1, PRX2 and PRX3 upregulated in response to treatment with yeast elicitor (YE). Metabolic profiling after induction with YE had shown the accumulation of hispidol and its corresponding 4-O-β-D-glucoside indicating a potential involvement of the three PRXs in the formation of those aurones [Farag09]. In vitro assays with recombinant PRX1, PRX2 and PRX3 and the starting substrate isoliquiritigenin resulted, in dependence of experimental conditions, in the formation of either hispidol catalyzed by PRX1 and PRX2 or 6-hydroxy-2-(4-hydroxy-phenoxymethylene)-benzofuran-3-one when PRX3 was tested. The same result for the three PRXs was obtained when isoliquiritigenin 4'-glucoside was used as substrate, i.e. the formation of hispidol-4'-O-β-D-glucoside by PRX1 and 2 and the yield of 6-hydroxy-2-(4-glucosyl-phenoxymethylene)-benzofuran-3-one by PRX3.

Although the reactions and reaction products between starting substrates isoliquiritigenin and isoliquiritigenin 4'-glucoside and the respective final products hispidol and 6-hydroxy-2-(4-hydroxy-phenoxymethylene)-benzofuran-3-one are hypothetical the reaction sequence is supported by findings in other studies. The formation of hispidol from isoliquiritigenin in Cicer arietinum [Wilson76a] and Glycine max [Wong66] including the identification of various intermediates was reported to be the result of the catalytic action of a dioxygenase which utilized hydrogen peroxide and oxygen to initiate the formation of intermediates which then were converted to the final product, i.e. hispidol via a non-enzymatic radical chain mechanism. In addition, the intermediate compounds 6-hydroxy-2-[hydroxy-(4-hydroxyphenyl)methyl]-1-benzofuran-3-one and 6-hydroxy-2-(6-oxo-1-oxaspiro[2.5]octa-4,7-dien-2-yl)-1-benzofuran-3-one of the above biosynthetic sequence had been previously identified in Glycine max as intermediates towards the formation of hispidol from isoliquiritigenin [Wong67].

The reaction mechanism of PRX1 and PRX2 in Medicago truncatula was proposed to involve the enzymatic formation of a specific neutral phenoxy radical [Altwicker67] from isoliquiritigenin that is further converted into hispidol by non-enzymatic steps of self-arrangements, intramolecular addition, cleavage and dehydration. However, the reaction sequence and the respective intermediates of the hispidol and hispidol 4'-O-β-D-glucoside biosynthesis remain to be elucidated. The obtained main product of the reaction(s), i.e. hispidol and hispidol-4'-O-β-D-glucoside by PRX1 and PRX2 in contrast to 6-hydroxy-2-(4-hydroxy-phenoxymethylene)-benzofuran-3-one and 6-hydroxy-2-(4-glucosyl-phenoxymethylene)-benzofuran-3-one formed by PRX3 has been explained by the varying optimal pH conditions for each enzyme which cause the diversion of the pathway at the potential common intermediate 2-[hydroperoxy(4-hydroxyphenyl)methyl]-6-hydroxy-1-benzofuran-3-one or its corresponding 4'-O-β-D-glucoside even though these reaction steps are propsed to be non-enzymatical. However, the products 6-hydroxy-2-(4-hydroxy-phenoxymethylene)-benzofuran-3-one and 6-hydroxy-2-(4-glucosyl-phenoxymethylene)-benzofuran-3-one have not been detected in Medicago and are therefore considered arteficial products of the in vitro reaction [Farag14].

Credits:
Created 08-Dec-2009 by Pujar A , Boyce Thompson Institute
Revised 03-Jan-2015 by Foerster H , Boyce Thompson Institute


References

Altwicker67: Altwicker ER (1967). "The chemistry of stable phenoxy radicals." Chemical reviews 67(5):475-531.

Farag09: Farag MA, Deavours BE, de Fatima A, Naoumkina M, Dixon RA, Sumner LW (2009). "Integrated metabolite and transcript profiling identify a biosynthetic mechanism for hispidol in Medicago truncatula cell cultures." Plant Physiol 151(3);1096-113. PMID: 19571306

Farag14: Farag, MA (2014). "personal communication 2014."

Frakas68: Frakas, L, Berenyl, E, Pallos, L (1968). "Aurones and aurone glucosides -XI synthesis of hispidol and its glucosides." Tetrahedron, 24, 4213.

Nakayama00: Nakayama T, Yonekura-Sakakibara K, Sato T, Kikuchi S, Fukui Y, Fukuchi-Mizutani M, Ueda T, Nakao M, Tanaka Y, Kusumi T, Nishino T (2000). "Aureusidin synthase: a polyphenol oxidase homolog responsible for flower coloration." Science 290(5494);1163-6. PMID: 11073455

Nakayama01: Nakayama T, Sato T, Fukui Y, Yonekura-Sakakibara K, Hayashi H, Tanaka Y, Kusumi T, Nishino T (2001). "Specificity analysis and mechanism of aurone synthesis catalyzed by aureusidin synthase, a polyphenol oxidase homolog responsible for flower coloration." FEBS Lett 499(1-2);107-11. PMID: 11418122

Wilson76a: Wilson JM, Wong E (1976). "Peroxidase catalysed oxygenation of 4,2',4'-trihydroxychalcone." Phytochemistry 15:1333-1341.

Wong66: Wong E (1966). "Occurrence and biosynthesis of 4',6-dihydroxyaurone in soybean." Phytochemistry 5:463-467.

Wong67: Wong E (1967). "Aurone biosynthesis-II. Formation of 4',6-dihydroxy-2-(α-hydroxybenzyl)coumaranone from 2',4,4'-trihydroxychalcone by cell-free extracts of soybean." Phytochemistry 6:1227-1233.

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

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

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547

Stich94: Stich K, Halbwirth H, Wurst F, Forkmann G (1994). "Formation of 6'-deoxychalcone 4'-glucosides by enzyme extracts from petals of Dahlia variabilis." Z. Naturforsch., 49c, 737-741.


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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
Page generated by SRI International Pathway Tools version 19.0 on Tue Jul 7, 2015, biocyc14.