Diversification of phenolic glucosides by two UDP-glucosyltransferases featuring complementary regioselectivity

作者：Fei Guo, Xingwang Zhang, Cai You, Chengjie Zhang, Fengwei Li, Nan Li, Yuwei Xia, Ming-Yu Liu, Zetian Qiu, Xianliang Zheng, Ma Li, Gang Zhang, Lianzhong Luo, Fei Cao, Yingang Feng, Guang-Rong Zhao, Wei Zhang, Shengying Li, Lei Du · 发表于：Microbial Cell Factories · 年份：2022 · DOI：10.1186/s12934-022-01935-w · 被引用次数：20 · 研究领域：Medicinal Plants and Bioactive Compounds、Plant Gene Expression Analysis、Biochemical and biochemical processes

BACKGROUND: Glucoside natural products have been showing great medicinal values and potentials. However, the production of glucosides by plant extraction, chemical synthesis, and traditional biotransformation is insufficient to meet the fast-growing pharmaceutical demands. Microbial synthetic biology offers promising strategies for synthesis and diversification of plant glycosides. RESULTS: In this study, the two efficient UDP-glucosyltransferases (UGTs) (UGT85A1 and RrUGT3) of plant origin, that are capable of recognizing phenolic aglycons, are characterized in vitro. The two UGTs show complementary regioselectivity towards the alcoholic and phenolic hydroxyl groups on phenolic substrates. By combining a developed alkylphenol bio-oxidation system and these UGTs, twenty-four phenolic glucosides are enzymatically synthesized from readily accessible alkylphenol substrates. Based on the bio-oxidation and glycosylation systems, a number of microbial cell factories are constructed and applied to biotransformation, giving rise to a variety of plant and plant-like O-glucosides. Remarkably, several unnatural O-glucosides prepared by the two UGTs demonstrate better prolyl endopeptidase inhibitory and/or anti-inflammatory activities than those of the clinically used glucosidic drugs including gastrodin, salidroside and helicid. Furthermore, the two UGTs are also able to catalyze the formation of N- and S-glucosidic bonds to produce N- and S-glucosides. CONCLUSIONS: Two highly efficient...