MODIFICATION OF THE ENZYME ENANTIOSELECTIVITY BY PRODUCT INHIBITION

A kinetic explanation of solvent effects on the enantioselective hydro lysis of racemic methyl and ethyl 2-chloropropionate by carboxylestera se NP has been studied. After a general ping-pong model for the kineti c resolution of chiral esters was defined, the progress curves of the reactions were analyzed, and a simplified uni-uni four-parameter model was selected. First-order rate constants and alcohol inhibition const ants were determined for both enantiomers. Enantiomeric excess values were correctly predicted from the model. According to the kinetic desc ription, the enantioselectivity could be enhanced or decreased by addi ng the product alcohol as a cosolvent. It appeared that these changes could be predicted quantitatively by enantioselective product inhibiti on for alcohol concentrations <10%. At higher alcohol concentrations a dditional changes in enantioselectivity occurred, which may be due to well-known changes in enzyme conformation, alteration of the solvent p roperties, or enzyme-solvent interactions. Similar results were found for hydrolyses catalyzed by alpha-chymotrypsin and Candida cylindracea lipase.