Asymmetric bioreduction of gamma- and delta-keto acids by native carbonyl reductases from Saccharomyces cerevisiae

Optically pure (R)-gamma- and (R)-delta-lactones can be prepared by intramolecular cyclization of chiral hydroxy acids/esters reduced asymmetrically from gamma- and delta-keto acids/esters using Saccharomyces cerevisiae (S. cerevisiae) as a whole-cell biocatalyst. However, some of the enzymes catalyzing these reactions in S. cerevisiae are still unknown up to date. In this report, two carbonyl reductases, OdCR1 and OdCR2, were successfully discovered, and cloned from S. cerevisiae using a genome-mining approach, and overexpressed in Escherichia coli (E. coli). Compared with OdCR1, OdCR2 can reduce 4-oxodecanoic acid and 5-oxodecanoic acid asymmetrically with higher stereoselectivity, generating (R)-gamma-decalactone (99% ee) and (R)-delta-decalactone (98% ee) in 85% and 92% yields, respectively. This is the first report of native enzymes from S. cerevisiae for the enzymatic synthesis of chiral gamma- and delta-lactones which is of wide uses in food and cosmetic industries. (C) 2020 The Authors. The Chemical Industry and Engineering Society of China, and Chemical Industry Press Co., Ltd. All rights reserved.

Automated summary

Two novel carbonyl reductases, OdCR1 and OdCR2, were discovered and overexpressed in Escherichia coli through genome-mining approach. OdCR2 showed higher stereoselectivity compared to OdCR1, efficiently synthesizing optically pure gamma- and delta-lactones.