Correlation between Intracellular Cofactor Concentrations and Biocatalytic Efficiency: Coexpression of Diketoreductase and Glucose Dehydrogenase for the Preparation of Chiral Diol for Statin Drugs

Abstract

Dynamic change of intracellular nicotinamide cofactor concentrations, the limiting factor for the bioreductions catalyzed by oxidoreductases, was monitored in Escherichia coli cells coexpressing diketoreductase and glucose dehydrogenase. On the basis of an unexpected observation, a relationship between catalytic efficiency and cofactor concentrations was established to optimize the process for the preparation of a chiral diol for statin drugs. Consequently, compared to previous reactions by E. coli cells expressing diketoreductase alone, exogenous addition of cofactors was completely eliminated to yield an increase of substrate concentration by 15-fold. The present strategy could be employed in the biocatalytic processes catalyzed by nicotinamide-dependent oxidoreductases.