Substrate range of acetohydroxy acid synthase I from Escherichia coli in the stereoselective synthesis of alpha-hydroxy ketones.
Acetohydroxy acid synthase I appears to be the most effective of the AHAS isozymes found in Escherichia coli in the chiral synthesis of phenylacetyl carbinol from pyruvate and benzaldehyde. We report here the exploration of a range of aldehydes as substrates for AHAS I and demonstrate that the enzyme can accept a wide variety of substituted benzaldehydes, as well as heterocyclic and heteroatomic aromatic aldehydes, to produce chiral carbinols. The active site of AHAS I does not appear to impose serious steric constraints on the acceptor substrate. The influence of electronic effects on the reaction has been probed using substituted benzaldehydes as substrates. The electrophilicity of the aldehyde acceptor substrates is most important to their reactivity, but the lipophilicity of substituents also affects their reactivity. AHAS I is an effective biosynthetic platform for production of a variety of alpha-hydroxy ketones, compounds with considerable potential as pharmacological precursors.
Engel
Stanislav
S
Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Vyazmensky
Maria
M
Berkovich
Dvora
D
Barak
Ze'ev
Z
Chipman
David M
DM
D000095:Acetolactate Synthase / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology*; D007659:Ketones / Q000138:chemical synthesis*; D007700:Kinetics; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013379:Substrate Specificity
D000447:Aldehydes; D007659:Ketones; D000095:Acetolactate Synthase