文献类型：期刊文献

英文题名：Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines

作者：Zhang, Man[1];Huang, Zheng-Yu[1];Su, Ying[1];Chen, Fei-Fei[1];Chen, Qi[1];Xu, Jian-He[1];Zheng, Gao-Wei[1]

机构：[1]East China Univ Sci & Technol, Coll Biotechnol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：10

期号：1

外文期刊名：BIORESOURCES AND BIOPROCESSING

收录：;EI(收录号：20231013665415);WOS:【SCI-EXPANDED(收录号:WOS:000942265400001)】；

基金：This work was financially supported by the National Key Research and Development Program of China (2019YFA09005000, 2021YFC2102800 and 2021YFA0911400), the National Natural Science Foundation of China (21878085, 31971380, 21472045 and 21871085), and the Fundamental Research Funds for the Central Universities (22221818014).

语种：英文

外文关键词：Biocatalysis; Norcoclaurine synthase; Protein engineering; Pictet-Spengler reaction; Tetrahydroisoquinoline alkaloids

摘要：Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet-Spengler (P-S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahydroisoquinoline alkaloids has attracted increasing attention due to their antitumor and antivirus activities. Herein, the L68T/M97V mutant of NCS from Thalictrum flavum with improved activity was developed by semi-rational design. This mutant not only showed higher catalytic performance (> 96% conversion) toward benzaldehyde and dopamine over the wild-type enzyme, but also catalysed the P-S reaction of the bulky substrate 4-biphenylaldehyde and dopamine with high conversion (> 99%) for the effective synthesis of 1-aryl-THIQA. In terms of stereoselectivity, all products synthesised by the L68T/M97V mutant showed high optical purity (92-99% enantiomeric excess).