Mechanistic Study of Enzymatic Reactions

6. Mechanistic Study of Enzymatic Reactions

Enzymatic reactions are currently being investigated in the Wong lab both due to their biological importance and for their application to chemical synthesis. Site-directed mutagenesis, 1H nuclear magnetic resonance and atomic-resolution x-ray structures have been utilized to study enzymatic catalysis. One such example is the aldol reaction catalyzed by Escherichia coli D-2-deoxyribose-5-phosphate (DERA, E.C. 4.1.2.4).

Figure 6A. DERA catalyzes the aldol reaction between an acetaldehyde donor and a D-glyceraldehyde-3-phosphate acceptor to generate DRP.

Figure 6B. The reversible aldol reaction between the donor aldehyde, acetaldehyde, and the acceptor substrate, D-glyceraldehyde-3-phosphate, generating D-2-deoxyribose-5-phosphate (DRP). Our interest in DERA is due in part to the aldol reaction's catalysis between two aldehydes as well as its high efficiency. Two critical water molecules involved in catalysis and enantioselective substrate binding were identified in our structure-mechanism study. Engineering this and other aldolases with broad substrate specificity also allows a much more environmentally friendly route to asymmetric aldol reactions than traditional chiral transition metal catalysis. (Science (2001) 294, 369)