Influence of Cofactor Regeneration Strategies on Preparative-Scale, Asymmetric Carbonyl Reductions by Engineered Escherichia coli

ABSTRACT: This study was designed to determine whether whole cells or crude enzyme extracts are more effective for preparative-scale ketone reductions by dehydrogenases as well as learning which cofactor regeneration scheme is most effective. Based on results from three representative ketone substrates (an α-fluoro-β-keto ester, a bis-trifluoromethylated acetophenone, and a symmetrical β-diketone), our results demonstrate that several nicotinamide cofactor regeneration strategies can be applied to preparative-scale dehydrogenase-catalyzed reactions successfully. Optically pure alcohols can be readily derivatized and further transformed, making them pivotal intermediates in asymmetric synthesis.1 Historically, catalytic hydrogenation has proven exceptionally useful in chiral alcohol synthesis,2,3 althoug