6 -deoxychalcones

The peptide sequences obtained for codeinone reductase aligned well with the amino acid sequences for 6 -deoxychalcone synthase (chalcone reductase) from alfalfa, Glycerrhiza, and soybean. Knowledge of the relative positions of the peptides allowed for a quick RT-PCR based isolation of cDNAs encoding codeinone reductase from P. somniferum. The codeinone reductase isoforms are 53 % identical to chalcone reductase from soybean.25 By sequence comparison, both codeinone reductase and chalcone reductase belong to the aldo/keto reductase family, a group of structurally and functionally related NADPH-dependent oxidoreductases, and thereby possibly arise from primary metabolism. Six alleles encoding codeinone... 

The stereospecific cyclization of chalcones to (2S)-flavanones is a prerequisite for the synthesis of the majority of fiavonoid subclasses derived from this branch point metabolite. This reaction is catalyzed by chalcone isomerase (CHI, CFI EC 5.5.1.6). CHI exists in two forms, one that accepts only 6 -hydroxychalcones and another that accepts both 6 -hydroxy-(naringenin chalcone) and 6 -deoxychalcones (isoliquirgentin), the latter generally found in legumes. Although 6 -hydroxychalcones will spontaneously convert to a racemic flavanone mixture, the CHI-catalyzed reaction proceeds at a rate 36 million-fold faster and is highly stereoselective for the formation of (25)-flavanones [60]. Spontaneous isomerization of 6 -deoxychalcones does not substantially occur without enzyme catalysis. 

This enzyme [EC 2.3.1.74] (also known as narmgenm-chalcone synthase, flavonone synthase, and 6 -deoxy-chalcone synthase) catalyzes the reaction of three malonyl-CoA with 4-coumaroyl-CoA to produce four coenzyme A, three carbon dioxide, and naringeninchal-cone. If both NADH and a particular reductase is also present, the final product is 6 -deoxychalcone. 

The structure of the recombinant M. sativa CHI-II protein has been determined to 1.85 A resolution. The progress of the reaction in the reactive site cleft has been elucidated, and a full reaction sequence proposed. However, the basis for the specificities toward 6 -hydroxy-and 6 -deoxychalcones was not resolved, although potentially key amino acid residues were identified. 

With 6 -hydroxychalcones, such as naringenin chalcone, the isomerization reaction can readily occur nonenzymically to form racemic (2R,2S) flavanone. This occurs easily in vitro and has been reported to occur in vivo to the extent that moderate levels of anthocyanin can be formed. However, 6 -deoxychalcones are stable under physiological conditions, due to an... 

A characteristic of legumes is the biosynthesis of 6 -deoxychalcones (chalcones lacking a hydroxyl at the C-6 position), which are the substrates for the production of 5-deoxyflavo-noids. The formation of 6 -deoxychalcones requires the activity of polyketide reductase (PKR) (also known as chalcone reductase or chalcone ketide reductase) in conjunction with CHS. It is thought that CoA-linked polyketide intermediates diffuse in and out of the CHS active site, and while unbound are reduced to alcohols by PKR. The resultant hydroxyl groups are then removed from the PKR products in the final cyclization and aromatization steps catalyzed by CHS. 

Tropf, S. et al., Reaction mechanisms of homodimeric plant polyketide synthases (stilbenes and chalcone synthase) a single active site for the condensing reaction is sufficient for synthesis of stilbenes, chalcones, and 6 -deoxychalcones. J. Biol. Chem., 270, 7922, 1995. 

Welle, R. and Grisebach, H., Phytoalexin synthesis in soybean cells elicitor induction of reductase involved in biosynthesis of 6 -deoxychalcone. Arch. Biochem. Biophys., 272, 97, 1989. 

Halbwirth, H. et al., Enzymatic glucosylation of 4-deoxyaurones and 6 -deoxychalcones with... 

FIGURE 16.3 Overview of the biosynthesis of (I) chalcones and (II) 6 -deoxychalcones. The sequential condensation of three molecules of malonyl-CoA (acetate pathway) and p-coumaroyl-CoA (shikimate pathway) is catalyzed by the enzyme chalcone synthase.The production of 6 -deoxychalcones is thought to involve an additional reduction step at the tri- or tetraketide level, catalyzed by polyketide reductase.The origin of the A-ring carbons derived from the acetate pathway is indicated in bold. CoA, coenzyme A. 

Wimmer, G. et al., Enz5matic hydroxylation of 6 -deoxychalcones with protein preparations from petals of Dahlia variabilis. Phytochemistry, 47, 1013, 1998. 

The main flavonoid skeleton derives from the stepwise condensation of three molecules of malonyl CoA with one molecule of 4-coumaroyl CoA, a reaction catalyzed by chalcone synthase (CHS) to form naringenin (2, 4,4 ,6,-tetrahydroxy) chalcone, the common intermediate in the formation of all flavonoids with 5,7-dihydroxy (flavone numbering) A-ring substitution. In some plants, however, an NADP-dependent chalcone-ketide reductase coacts with CHS to form 6 -deoxychalcone, the precursor of 5-deoxyflavonoids. The resulting chalcones undergoe a stereospecific cyclization to the corresponding (2S) flavanones, the... 

Microsomal preparations of Dahlia variabilis flowers have been reported to catalyze the 3-hydroxylation of the 6 -deoxychalcone, isoliquiritigenin, to butein.46 This enzyme activity was shown to be a typical cytochrome P450 monooxygenase that appears to be different from the F3 H, although its occurrence in other species remains to be investigated. 

Ayabe, S., A. Udagawa, and T. Furuya Studies on Plant Tissue Cultures. 54. NAD(P)H-Dependent 6 -Deoxychalcone Synthase Activity in Glycyrrhiza echinata Cells Induced by Yeast Extract. Arch. Biochem. Biophys., 261, 458 (1988). 

Harano, K., N. Okada, T. Furuno, T. Takahashi, S. Ayabe, and R. Welle Enzymatic Synthesis of 6 -Deoxychalcone in Cultured Glycyrrhiza echinata Cells. Plant Cell Rep., 12, 66 (1993). 

Discrete plant KRs have been identified that interact with CHS for the biosynthesis of 6 -deoxychalcone (20) (Fig. 3D) [133, 136-139]. Interestingly, the plant KR has no similarity with those that catalyze the reduction of the poly- -ketone intermediates in polyketide or fatty acid biosynthesis [49, 50, 81-84]. Instead it is similar to various aldo/keto-reductases, mostly from carbohydrate metabolism [139-141], and contains a leucine zipper motif known to be involved in protein-protein interaction [142]. Plant 0-methyltransferases are well known [143], but enzymes for C-methylation have not been described. The... 

Fig. 10A-D. Pathways for plant polyketide synthase catalyzed biosynthesis of A chalcone and stilbene B 6 -deoxychalcone C methylchalcone D 2-pyrone...

Chalcones were originally discovered in plants as the yellow flower pigments of Coreopsis and other yellow-rayed Compositae. After that, they have subsequently been found in other plant families including Solanaceae, Anacardiaceae, Caesalpiniaceae, Piperaceae, and Apiaceae. 6 -Deoxychalcones were known to be chemical constituents of leguminous plants, but it is scarcely reported that they were found in other plant species. A lot of chalcones were isolated from either Compositae (Asteraceae) or Leguminosae (Fabaceae), two families well known to accumulate these. Besides, various prenylchalcones can be found in hop plants (Cannabaceae). 

Fig. 2.5 Biosynthetic routes to flavonoids and 5-deoxyflavonoids in the Leguminosae. CHS, chalcone synthase CHR, chalcone reductase CHI, chalcone isomerase IFS, isoflavone synthase. The acetate-derived A-ring carbon atoms of chalcones and 6 -deoxychalcones are indicated in bold.

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