Chalcone synthase reaction products

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 key reaction of flavonoid biosynthesis, the condensation of the acyl residues from one molecule of 4-coumaroyl-CoA and three molecules of malonyl-CoA, previously had been assumed to be catalysed by a flavonone synthase . Studies by Heller and Hahlbrock (1980) indicated that the immediate product of the synthase reaction was not the flavonone but the isomeric chalcone. The term chalcone synthase was therefore suggested for the enzyme. 

Rg.6. Reactions catalyzed by chalcone and stilbene synthases. Each enzyme condenses three malonyl CoA extender units onto p-coumaroyl-CoA. Stilbene synthases catalyze an additional decarboxylation, resulting in a different pattern of cyclization for chalcone versus stilbene products... 

Type III synthases, as a whole, employ a wider spectrum of physiological starter molecules than their type I and II counterparts, including a variety of aromatic and aliphatic CoA esters such as coumaiyl-CoA, methyl-anthraniloyl-CoA, as well as the recently identified medium- and long-chain fiitty acyl-CoA ester starters used by certain bacterial and plant type III enzymes involved in the biosyndiesis of phenolic lipids (22, 24, Cook et al., unpublished results). The most extensively studied type III en mie, chalcone synthase (Fig. 4), uses 4-coumaryl-CoA as the starter unit and catalyzes three successive condensation reactions with malonyi-CoA as the extender. Cyclization and aromatization of the linear tetraketide intermediate is performed within the same active site, yielding the final product 4 ,2 ,4 ,6 -tetrahydroxychalcone. 

Figure 1. Type III polyketide synthases and their reaction products. CHS chalcone synthase, STS stilbene synthase BPS benzophenone synthase ACS acridone synthase VPS valerophenone synthase CTAS p-coumaryltriacetic acid synthase 2PS 2-pyrone synthase SPS styrylpyrone synthase BAS benzalacetone synthase H/EDS homoeryodyctiol/eriodyctiol chalcone synthase ALS Aloesone synthase PCS phertylchromone synthase BIS biphenyl synthase...

Flavonoids are a large class of plant natural products of low molecular weight. Over 3,000 different flavonoids have been chemically characterised and novel ones are still being reported. Flavonoids are aromatic molecules synthesised from the amino acid phenylalanine and an acetate-derived precursor as malonyl-coenzyme A (Fig. 11.1) (Winkel-Shirley 2001). This reaction is carried out by the enzyme chalcone synthase (CHS) to produce chalcone. The chalcone can subsequently be isomerised by the enzyme chalcone flavone isomerase (CHI) to yield a flavanone. From these intermediates the pathway diverges into several side branches yielding different subclasses of flavonoids, as summarised in Fig. 

Type I and Type II PKSs catalyze multiple rounds of reactions by catalytic modules encoded either by a single polypeptide (PKS I) or on separate polypeptides (PKS II) by analogy to FAS-I and FAS-II. In contrast, PKS Ills are dimers of KASs that catalyze multiple condensation reactions in one active site and include chalcone synthase, stilbene synthase, and 2-pyrone synthase (see Chapters 1.05, 1.07, and 1.04). In the case of chalcone synthase, three consecutive condensation reactions each utilizing malonyl-CoA, followed by a cyclization reaction, lead to the formation of 4, 2, 4, 6 -tetrahydroxychalcone from 4-hydroxycinnamoyl-CoA (Figure 3). Recruitment of a reductase leads to the formation of a product lacking the 6 -hydroxy group, a reaction that requires an intermediate in the synthesis of chalcone to dissociate from the synthase active site. 

The biosynthetic pathway for isoflavonoids in soybean and the relationship of the isoflavonoids to several other classes of phenylpropanoids is presented in Fig. 8.2. Production of /i-coumaryl-CoA from phenylalanine requires phenylalanine ammonia lyase to convert phenylalanine to cinnamate, cinnamic acid hydroxylase to convert cinnamate to /7-coumarate, and coumaraterCoA ligase to convert jt -coumarate to -coumaroyl-CoA. Lignins may be produced from j3-coumaroyl-CoA or from />-coumarate. Chalcone synthase catalyzes the condensation of three molecules of malonyl CoA with p-coumaroyl-CoA to form 4, 2 , 4 , 6 -tetrahydroxychalcone, which is subsequently isomerized in a reaction catalyzed by chalcone isomerase to naringenin, the precursor to genistein, flavones, flavonols, condensed tannins, anthocyanins, and others. 

Mutants that lack chalcone isomerase, the next enzyme in the sequence, accumulate chalcones, not flavanones, and establish that the initial product of the reaction is a chalcone (Grisebach, 1985). Recessive genotypes of certain flowers that lack chalcone synthase accumulate cinnamic acid gluco-sides (Grisebach, 1985). 

Many polyketide-derived plant natural products originate in part from acetyl CoA via malonyl CoA (Fig. 1). For example, the key reaction in flavonoid biosynthesis, catalyzed by chalcone synthase (CHS) (Fig. 2), combines a phenylpro-panoid-derived moiety, 4-coumaroyl CoA, with three molecules of malonyl CoA. Although acetyl CoA carboxylase, the enzyme forming malonyl CoA, is essentially an enzyme of primary metabohsm (Fig. 1), it is often co-regulated with the enzymes of plant polyketide biosynthesis [8]. 

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