Pyruvate-dependent aldolases structure

The aldolases which have been investigated for their synthetic utility can be classified on the basis of the donor substrate accepted by the enzyme. For the synthesis of 3-deoxy-2-ulosonic acids pyruvate- and phosphoenolpyruvate dependent aldolases are the most desirable enzymes as they are involved in the metabolism of sialic acids (or structurally related ones) in vivo. They use pyruvate or phosphoenolpyruvate as a donor to form 3-deoxy-2-keto acids (Table 1). Both of them add a three-carbons ketone fragment onto a carbonyl group of an aldehyde. The pyruvate dependent aldolases have a catabolic function in vivo, whereas the phosphoenolpyruvate dependent aldolases are involved in the biosynthesis of the keto acids. For synthetic purpose the equilibrium of the pyruvate dependent aldolases is shifted toward the condensation products through the use of an excess of pyruvate. 

A convenient chemoenzymatic access to sialic acid mimetics as important inhibitors of influenza sialidases has been established by Nelson et al. (Fig. 35b) [191, 192]. Application of a pyruvate-dependent sialic acid aldolase improved by directed evolution disclosed a new route to the core structure of important pharmaceuticals, such as zanamivir (Relenza ). 

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