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.