文献类型：期刊文献

英文题名：Continuous-flow synthesis of polysubstituted γ -butyrolactones via enzymatic cascade catalysis

作者：Chu, Liliang[1];Zhang, Xiaoyan[1];Li, Jianing[1];Deng, Xuelei[1];Wu, Miao[2];Cheng, Ya[2];Zhu, Weiping[1];Qian, Xuhong[1];Bai, Yunpeng[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Sch Phys & Mat Sci, Extreme Optoelectromechan Lab, Shanghai 200241, Peoples R China

年份：2024

卷号：35

期号：4

外文期刊名：CHINESE CHEMICAL LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001170948500001)】；

基金：This work was financially sponsored by the National Key Re- search and Development Program of China (No. 2021YFC2102804) and the National Natural Science Foundation of China (No. 22078096) .

语种：英文

外文关键词：Enzyme catalysis; Cascade catalysis; Directed evolution; Continuous-flow; gamma -Butyrolactones

摘要：Polysubstituted chiral gamma-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis of these molecules faces the problems of low enzyme activity and phase separation in batch reaction, resulting in low productivity. Herein, we report a new continuous-flow process to synthesize the optically pure Nicotiana tabacum lactone (3S,4S)-4a and whisky lactone (3R,4S)-4b from alpha,beta-unsaturated gamma-ketoesters. A new ene reductase (ER) from Swingsia samuiensi (SsER) and a carbonyl reductase (SsCR) were engineered by directed evolution to improve their activity and thermostability. The continuous-flow preparative reactions were performed in two 3D microfluidic reactors, generating (3S,4S)-4a (99% ee and 87% de ) and (3R,4S)-4b (99% ee and 98% de ) with space-time yields 3 and 7.4 times higher than those of the batch reactions. The significant enhancement in the productivity of enzyme cascade catalysis brought by cutting-edge continuous microfluidic technology will benefit the general multi-enzyme catalytic systems in the future. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.