Asymmetric DHAP-dependent aldolases

The four enzymes of the family of dihydroxyacetone phosphate (DHAP)-dependent aldolases fructose-1,6-bisphosphate aldolase (FruA, EC 4.1.2.13), fuculose-1-phosphate aldolase (FucA, EC 4.1.2.17), rhamnulose-1-phosphate aldolase (RhuA, EC 4.1.2.19) and tagatose-1,6-bisphosphate aldolase (TagA, EC 4.1.2.40), catalyze in vivo the reversible asymmetric addition of DHAP to d-glyceraldehyde-3-phosphate (G3P) or L-lactaldehyde, leading to four complementary diastereomers. DHAP-dependent aldolases create two new stereogenic centers, with excellent enantio and diastereoselectivity in many cases. These enzymes are quite specific for the donor substrate DHAP, but accept a wide range of aldehydes as acceptor substrates. There are only two fructose-6-phosphate aldolase isoenzymes reported to be able to use dihydroxyacetone (DHA) as donor substrate (Schiirmann and Sprenger 2001). 

DHAP-dependent aldolases constitute a major group of aldolases. Indeed, it exhibits a broad scope of possible aldehyde acceptors. Moreover, the stereochemical configuration of the two newly formed asymmetric centers can be controlled by choosing one of the four stereocomplementary DHAP aldolases. They are distinguished in two different classes presenting two different types of action and mechanism. The type 1... 

While the lyases that transfer a pyruvate unit form only a single stereogenic center, the group of dihydroxyacetone-phosphate-(DHAP, 41)-dependent aldolases create two new asymmetric centers, one each at the termini of the new C-C bond. A particular advantage for synthetic endeavors is the fact that Nature has evolved a full set of four stereochemically-complementary aldolases [189] (Scheme 6) for the retro-aldol cleavage of diastereoisomeric ketose 1-phosphates— D-fructose 1,6-bisphosphate (42 FruA), D-tagatose 1,6-bisphosphate (43 TagA), L-fuculose 1-phosphate (44 FucA), and L-rhamnulose 1-phosphate (45) aldolase (RhuA). In the direction of synthesis this formally allows the... 

With respect to practical applications in asymmetric synthesis, the four stereo-chemically distinct dihydroxyacetone phosphate (DHAP, 1)-dependent enzymes had been particularly appealing to us because these enzymes control the creation of two new asymmetric centers at the termini of a newly formed C-C bond, thus allowing an effective stereocombinatorial synthesis of stereoisomers (Scheme 2.2.5.1) [1, 3]. The individual aldolases are involved in the reversible cleavage of... 

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