文献类型：期刊文献

英文题名：Enantioselective synthesis of structurally diverse aryl γ-/δ- lactones using an engineered carbonyl reductase

作者：Lu, Zhiwen[1];Liu, Jiaxu[1];Zhang, Xiaoyan[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

年份：2023

卷号：200

外文期刊名：BIOCHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20233814767900);WOS:【SCI-EXPANDED(收录号:WOS:001145305900001)】；

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

语种：英文

外文关键词：Carbonyl reductase; Directed evolution; Asymmetric reduction; Chiral aryl lactones

摘要：Optically pure aryl gamma-/delta-lactones are valuable building blocks in the organic synthesis of natural products and pharmaceutical compounds. The asymmetric reduction of aryl keto acids or esters using carbonyl reductase provides a green and atom-economic synthetic route to these molecules. However, this method is still challenging due to the substantial steric hindrance of substrates, which has limited its practical application. Herein, we report the engineering of a carbonyl reductase SmCRV4, which showed excellent enantioselectivity (99% (S)) for methyl 3-benzoyl propionate (1a), to obtain the mutant SmCRW6 by directed evolution. The specific activity and catalytic efficiency of SmCRW6 towards 1a were 4.9-fold and 3.2-fold higher than those of the parent SmCRV4, respectively. The mutant SmCRW6 showed a broad substrate scope (26 examples) with improvement in specific activity and enantioselectivity for most substrates. Finally, 7 chiral aryl lactones and 10 aliphatic lactones were prepared using lyophilized enzyme powder. In scaled-up synthesis, three aryl gamma-/delta-lactones were prepared with > 97% conversions, 76 - 88% yields and ee up to > 99%, and the highest space-time yield (STY) of 28.2 g L-1 h(-1) reported so far for (S)-gamma-phenyl-gamma-butyrolactone was obtained through biocatalysis.