Highly Efficient Asymmetric Synthesis of Aliphatic Chiral Secondary Alcohols by Whole Cells of E. coli Co-Expressing Alcohol Dehydrogenase and Glucose Dehydrogenase

Abstract

Aliphatic chiral secondary alcohols are important chiral intermediates widely used in the synthesis of drugs and fine chemicals. The whole cells of recombinant E. coli co-expressing alcohol dehydrogenase and glucose dehydrogenase were used to catalyze the asymmetric reduction of three fatty ketones without the addition of exogenous cofactors. The reaction medium and reaction conditions were systematically studied. As expected, the kinds of co-solvents, the molar ratio of glucose/substrate, temperature, pH and cell amount have important influence on the reaction. Under the optimal condition (glucose at 1.5 times substrate concentration, isopropanol at 2%, PBS (0.1 M, pH 8.0), and 45℃), the cells co-expressing both enzymes efficiently catalyzed the asymmetric reduction of three fatty ketones to the corresponding (S)-fatty alcohols. The conversion and ee value of the products were both greater than 99% after 8 h reaction at 1 M of substrate concentration, and the space-time yield was between 346 ~ 470 g/(L·d). All the products can be obtained on gram scale. The results indicated that this method has potential application value in the efficient and green synthesis of aliphatic chiral secondary alcohols.

Graphical Abstract