This study aimed to develop a biotransformation process for the production of (S)-1-[2-(trifluoromethyl)phenyl]ethanol, a key chiral intermediate of Plk1 inhibitor, and increase its productivity through medium engineering strategy. A fungus isolate Geotrichum silvicola ZJPH1811 was adopted as biocatalyst for 2ʹ-(trifluoromethyl)acetophenone reduction, and gave the best performance with > 99.2% product ee. To improve the yield, choline acetate/cysteine (ChAc/Cys) was introduced as co-solvent in reaction system, which accelerated mass transfer and protected cells from substrate inhibition. Moreover, a synergistic effect of methylated-β-cyclodextrin (MCD) and ChAc/Cys was found in the bioreduction, with further enhancement in substrate concentration and cell membrane permeability. Compared with buffer system, in the developed ChAc/Cys-MCD-containing system, substrate loading and product yield were increased by 6.7-fold and 2.4-fold respectively. This is the first report on (S)-1-[2-(trifluoromethyl)phenyl]ethanol production with G. silvicola, and provides valuable insight into the synergistic effect of DES and CDs in biocatalysis.

这项研究旨在开发一种生物转化工艺，以生产（S）-1- [2-（三氟甲基）苯基]乙醇（Plk1抑制剂的关键手性中间体），并通过中等工程策略提高其生产率。真菌分离土GeoZJPH1811被用作还原2′-（三氟甲基）苯乙酮的生物催化剂，并以> 99.2％的产品ee表现出最佳性能。为了提高收率，将乙酸胆碱/半胱氨酸（ChAc / Cys）作为助溶剂引入反应体系中，从而加速了质量转移并保护了细胞免受底物抑制。此外，在生物还原中发现了甲基化的β-环糊精（MCD）和ChAc / Cys的协同作用，并进一步提高了底物浓度和细胞膜通透性。与缓冲系统相比，在开发的含ChAc / Cys-MCD的系统中，底物负载和产物收率分别增加了6.7倍和2.4倍。这是关于G. silvicola生产（S）-1- [2-（三氟甲基）苯基]乙醇的第一份报告，并提供有关DES和CD在生物催化中的协同作用的宝贵见解。