Continuous-flow synthesis of polysubstituted γ-butyrolactones via enzymatic cascade catalysis  

作　　者：Liliang Chu Xiaoyan Zhang Jianing Li Xuelei Deng Miao Wu Ya Cheng Weiping Zhu Xuhong Qian Yunpeng Bai 

机构地区：[1]State Key Laboratory of Bioreactor Engineering,Shanghai Collaborative Innovation Center for Biomanufacturing,East China University of Science and Technology,Shanghai 200237,China [2]The Extreme Optoelectromechanics Laboratory,School of Physics and Materials Science,East China Normal University,Shanghai 200241,China

出　　处：《Chinese Chemical Letters》2024年第4期404-408,共5页中国化学快报（英文版）

基　　金：financially sponsored by the National Key Research and Development Program of China (No.2021YFC2102804);the National Natural Science Foundation of China(No.22078096)。

摘　　要：Polysubstituted chiral γ-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 α,β-unsaturatedγ-ketoesters. A new ene reductase(ER) from Swingsia samuiensi(Ss ER) and a carbonyl reductase(Ss CR)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 and87% 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.

关 键 词：Enzyme catalysis Cascade catalysis Directed evolution CONTINUOUS-FLOW γ-Butyrolactones 

分 类 号：TQ235[化学工程—有机化工] O643.36[理学—物理化学]