New Strategy for Effective Biosynthesis of Chiral Aryl Alcohols: Co-Cultivation Microbe with Natural Deep-Eutectic Solvent

In this study, a new strategy was developed for efficient synthesis of chiral aryl alcohols mediated by permeabilizing whole-cell catalyzed bioreduction. The permeabilized biocatalyst was prepared via co-cultivation microbial cells with natural deep-eutectic solvent (NADES) in their growth period, and the bioreductive efficiency was significantly enhanced due to the improvement of cell permeability for overcoming mass-transfer limitation in the reduction of prochiral ketones. This approach was successfully employed in the model reaction of 2-chloro-1-(3,4-difluorophenyl)ethanone to (S)-2-chloro-1-(3,4-difluorophenyl)ethanol [(S)-CFPL] with newly isolated Geotrichum candidum ZJPH1907 in a Tween 80-containing buffer system. Compared to the conventional NADES addition in reaction system as co-solvent, a much higher catalytic yield (98.7% vs 62.5%) was achieved with good enantioselectivity via a co-cultivation strategy, in which the permeabilizing biocatalyst was obtained by co-incubation G. candidum cells with 0.5% (w/v) choline chloride/lysine (ChCl/Lys) (molar ratio 1:2). The developed new strategy was concise, feasible, and eco-friendly through the analysis of green chemistry metric, and the catalytic efficiencies were also enhanced in the bioreduction of other aryl ketones. This work provides a new understanding of NADES in biocatalysis and broadens its application.