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 > 60% 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 μm. Large specific surface area provided high mass transfer efficiency between phases. While the analogous reaction in a traditional stirred tank required > 270 min to achieve a yield of > 99%, in this biphasic microreaction system, the yield reached 99.6% with a high enantiomeric excess (ee) of > 99% in only 80 min. Efficient synthesis was achieved by reducing the time by 70%.