糖基转移酶
糖基化
糖苷
化学
酶
生物化学
基质(水族馆)
立体化学
生物
生态学
作者
Kebo Xie,Xiaolin Zhang,Songyang Sui,Fei Ye,Jungui Dai
标识
DOI:10.1038/s41467-020-18990-9
摘要
Abstract Bioactive natural C -glycosides are rare and chemical C -glycosylation faces challenges while enzymatic C -glycosylation catalyzed by C -glycosyltransferases provides an alternative way. However, only a small number of C -glycosyltransferases have been found, and most of the discovered C -glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C -glycosyltransferase, AbCGT, which is capable of C -glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis . Based on the substrate promiscuity of AbCGT, 16 C -glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C -glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L ‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C -glycosyltransferases.
科研通智能强力驱动
Strongly Powered by AbleSci AI