Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
Bioresour Technol. 2021 Jun;329:124832. doi: 10.1016/j.biortech.2021.124832. Epub 2021 Feb 12.
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 2'-(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.
本研究旨在开发一种生物转化工艺，用于生产（S）-1-[2-（三氟甲基）苯基]乙醇，这是 Plk1 抑制剂的关键手性中间体，并通过培养基工程策略提高其生产力。真菌分离株 Geotrichum silvicola ZJPH1811 被用作 2' - （三氟甲基）苯乙酮还原的生物催化剂，产物的对映体过量值（ee）超过 99.2%。为了提高产率，在反应体系中引入了乙酸胆碱/半胱氨酸（ChAc/Cys）作为共溶剂，这加速了质量传递并保护细胞免受底物抑制。此外，在生物还原中发现了甲基化-β-环糊精（MCD）和 ChAc/Cys 的协同作用，进一步提高了底物浓度和细胞膜通透性。与缓冲体系相比，在开发的含有 ChAc/Cys-MCD 的体系中，底物负荷和产物产率分别提高了 6.7 倍和 2.4 倍。这是首次报道利用 Geotrichum silvicola 生产（S）-1-[2-（三氟甲基）苯基]乙醇，为 DES 和 CDs 在生物催化中的协同作用提供了有价值的见解。
