Stilbenes, polyketide-derived

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

SCHRODER, J., The chalcone/stilbene synthase-type family of condensing enzymes. In Comprehensive Natural Products Chemistry, vol. 1, Polyketides and Other Secondary Metabolites Including Fatty Acids and Their Derivatives (U. Sankawa ed.), Elsevier, Amersterdam, 1999, pp. 749-771. 

Stilbenoids are derived from cinnamic acid and three acetate units from mal-onyl coenzym A. The first part of the biosynthesis is in common to flavonoids. The two biosynthetic routes are diverging at the point of cyclization of a styryl-3,5,7-triketoheptanoic acid. A C-acylation produces a chalcone and subsequent modifications lead to the flavonoids. An aldol condensation of the same intermediate polyketide produces a stilbene-2-carboxylic acid that is unstable and constitutes a range of structures known as stilbenoids. Figure 9C.5 shows an overview of the biosynthetic pathway (Gorham 1995). 

Type III polyketide synthases are responsible for the biosynthesis of a vast number of plant-derived natural products, including flavonoids derived from the important branch metabolite 4 ,2 ,4 ,6 -tetrahydroxychalcone, the product of the enzyme chalcone synthase (39). Because chalcone synthase was the first type III enzyme discovered, and a second flavonoid pathway type III enzyme, stilbene synthase, was discovered shortly thereafter, type III PKSs are also collectively referred to as the chalcone synthase/stilbene synthase superfamily of enzymes (24,25). 

J. Schroder, The Chalcone/Stilbene Synthase-Type Family ot Condensing Enzymes. In Oomprehensive Natural Products Chemistry, Vol. 1 Polyketides and Other Secondary Metabolites Including Fatty Acids and Their Derivatives U. Sankawa, Ed. Sir D. H. R. Barton, K. Nakanishi, O. Meth-Cohn, Series Eds. Elsevier Oxford, 1999 pp 749-771. 

Addition. Resveratrol. The biosynthetic pathway to resveratrol diverges from the flavonoid pathway after the third malonyl-CoA condensation. Cyclization of the common polyketide intermediate catalyzed by resveratrol synthase yields the stilbene derivative resveratrol, whereas the same intermediate catalyzed by chal-cone synthase yields the common flavonoid precursor chalcone (Fig. 6.8). Resveratrol, well known as a functional food ingredient (e.g., grape skin, red wine) with strong antioxidant properties (cardiovascular protection), and its 3-glucopyranoside piceid turned out to be also present in the skin of tomato fruits, S. lycopersicum (Ragab et al. 2006). 

Fig. 3.6. Idealized biosynthetic scheme [adapted in part from ref. (52)] for some acetate-derived [chain initiation by acetate (R = methyl represented by Me), chain continuation by malonate] and for some cinnamate-acetate-derived [chain initiation by cinnamate (R = styryl represented by St), chain continuation by malonate] classes of secondary metabolites. The enzyme surface, through its thiol terminals, is postulated to bring the reactants into appropriate vicinity for chain formation. Specific forms of the enzyme surfaces are idealized to lead either to flavonoids, stilbenes, and 6-styrylpyrones or to three types of polyketides according to the nature of R...

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