Whole-cell biocatalytic synthesis of S-(4-chlorophenyl)-(pyridin-2-yl) methanol in a liquid-liquid biphasic microreaction system.

Abstract

This work aims to synthesize S-(4-chlorophenyl)-(pyridin-2-yl) methanol (S-CPMA) in a green, economic, and efficient way. In the water-cyclohexane liquid-liquid system, recombinant Escherichia coli (E. coli) was used as a whole-cell catalyst and retained\xa0>\xa060% of its catalytic activity after five reuse cycles. In situ accumulation of the substrate/product in the organic phase effectively improves substrate tolerance and reduces product inhibition and toxicity. Meanwhile, a microreaction system consisting of membrane dispersion and three-dimensional (3D) bending-microchannel was developed to successfully generate droplet swarms with an average diameter of 30\xa0μm. Large specific surface area provided high mass transfer efficiency between phases. While the analogous reaction in a traditional stirred tank required\xa0>\xa0270\xa0min to achieve a yield of\xa0>\xa099%, in this biphasic microreaction system, the yield reached 99.6% with a high enantiomeric excess (ee) of\xa0>\xa099% in only 80\xa0min. Efficient synthesis was achieved by reducing the time by 70%.