Chalcone synthase reactions catalyzed

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. 

FIGURE 16.S Reactions catalyzed by the plant polyphenol oxidase, aureusidin synthase (AS), in the transformation of chalcones to aurones. (A) The biosynthesis of aureusidin from either tetra- or pentahydroxychalcone precursors through an ortho-diqmnone intermediate. (B) The aureusidin synthase-catalyzed formation of bracteatin from a pentahydroxychalcone precursor. 

Flavonoid biosynthesis (Figure 3-7) is initiated from the condensation of / -coumaroyl-CoA (3.31) with three molecules malonyl-CoA (3.48), which is catalyzed by the enzyme chalcone synthase (CHS), and gives rise to 4,2, 4, 6 tetrahydroxychalcone (3.49). This compound can undergo a number of reactions that give rise to the different classes of compounds described in Section 3.6 of Chapter 1. 

Fig. 1. Simplified diagram of the phenylpropanoid and flavonoid biosynthetic pathways. Enzymes that catalyze the reactions are placed on the left-hand side, and transcription factors on the right-hand side of the arrows. Both transcription factors for which their control over the enzymatic steps has been genetically proven, as well as transcription factors that have been shown to interact with promoters of the structural genes, are shown. PAL Phenylalanine ammonia lyase C4H cinnamate 4-hydroxylase 4CL 4-coumaroyl-coenzyme A ligase CHS chalcone synthase CHI chalcone-flavanone isomerase F3H flavanone 3(3-hydroxylase DFR dihydroflavonol 4-reductase AS anthocyanin synthase UFGT UDP glucose-flavonol glucosyl transferase RT anthocyanin rhamnosyl transferase...

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... 

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. 

BPS catalyzed the stepwise condensation of benzoyl-CoA with three molecules of malonyl-CoA to give a tetraketide intermediate that was cyclized by intramolecular Claisen condensation into 2,4,6-trihydroxybenzophenone (Figure 2). The enzyme was inactive with CoA-linked ciimamic acids such as 4-coumaroyl-CoA, the preferred starter substrate for chalcone synthase (CHS). BPS and CHS from H. androsaemum cell cultures shared 60.1% amino acid sequence identity. CHS is ubiquitous in higher plants and the prototype enzyme of the type III PKS superfamily (1,2). It uses the same reaction mechanism like BPS to form 2, 4,4, 6 -tetrahydroxychalcone, the precursor of flavonoids (Figure 2). 

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. 

Alternatively, chalcone reductase (CHR also known as deoxychalcone synthase) together with chalcone synthase and NADPH as a cofactor act in the formation of isoliquiritigenin, which is then isomerized, again by the enzyme chalcone isomerase, to form liquiritigenin, the precursor to daidzein, and the pterocarpan phytoalexins. A type II chalcone isomerase that seems to be found exclusively in the legumes catalyzes this isomerization reaction. Glycitein synthesis is not yet clearly defined, but is likely derived from liquiritigenin via flavonoid 6-hydroxylase, and an unidentified methyltransferase. 

Chalcone synthases (CHS) and stilbene synthase (STS) are closely related plant PKSs that catalyze the stepwise condensation between acyl CoA esters in the biosynthesis of flavonoids, stilbenes, and other related plant aromatic polyke-tides [70,72,75]. Sequences for munerous CHS as well as a few STS have been determined from various plants [72-76, 122-131]. They all possess a highly conserved cysteine (Cys) residue that is essential for PKS activity, although the sequences in this Cys motif have no apparent similarity to that of KS of bacterial and fungal PKSs [ 132]. The plant PKSs are essentially condensing enzymes,lack the ACP domain, and use the acyl CoA esters directly as substrate for the condensing reactions [72,75]. 

Fig. 27. Reactions catalyzed by stilbene synthase and by chalcone synthase. Reprinted, with modifications, from Reference 46 with permission of the American Society of Plant Physiology.

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]. 

Fig. 2 Reaction types catalyzed by plant type III polyketide synthases. PS, pyrone synthase CHS, chalcone synthase STS, stilbene synthase VPS, valerophenone synthase ACS, acridone synthase BPS, benzophe-none synthase...

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