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

被引：9

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

来源：

CHINESE CHEMICAL LETTERS | 2024年 / 35卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Enzyme catalysis; Cascade catalysis; Directed evolution; Continuous-flow; gamma; -Butyrolactones;

D O I：

10.1016/j.cclet.2023.108896

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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.

引用

页数：5

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[1] The enriched fraction of Elephantopus scaber Triggers apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells [J].