Aldolases class 11, stereochemistry

The transaldolase (EC 2.2.1.2) is an ubiquitous enzyme that is involved in the pentose phosphate pathway of carbohydrate metabolism. The class I lyase, which has been cloned from human [382] and microbial sources [383], transfers a dihydroxyacetone unit between several phosphorylated metabolites. Although yeast transaldolase is commercially available and several unphosphorylated aldehydes have been shown to be able to replace the acceptor component, preparative utilization has mostly been limited to microscale studies [384,385] because of the high enzyme costs and because of the fact that the equilibria usually are close to unity. Also, the stereochemistry of transaldolase products (e.g. 38, 40) [386] matches that of the products from the FruA-type DHAP aldolase which are more effortlessly obtained. 

Mechanistically, the activation of the aldol donor substrates is achieved by stereospecific deprotonation along two different pathways (Fig. 2) [28] Class I aldolases bind their substrates covalently via imine/enamine formation to an active site lysine residue to initiate bond cleavage or formation (Fig. 2a) in contrast, class II aldolases utilize transition metal ions as a Lewis acid cofactor (usually Zn " ) which facilitates (Fig. 2b) deprotonation by a bidentate coordination of the donor to give the enediolate nucleophile [29]. Usually, the approach of the aldol acceptor to the enzyme-bound nucleophile occurs stereospecif-ically following an overall retention mechanism, while the facial differentiation of the aldehyde carbonyl is responsible for the relative stereoselectivity. In this manner, the stereochemistry of the C—C bond formation is completely controlled by the enzyme, in... 

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