Effective Generation of Glucosylpiericidins with Selective Cytotoxicities and Insights into Their Biosynthesis.

ABSTRACT: Exploring unknown glycosyltransferases (GTs) is important for compound structural glycodiversification during the search for drug candidates. Piericidin glycosides have been reported to have potent bioactivities; however, the GT responsible for piericidin glucosylation remains unknown. Herein, BmmGT1, a macrolide GT with broad substrate selectivity and isolated from Bacillus methylotrophicus B-9987, was found to be able to glucosylate piericidin A1 in vitro. Next, the codon-optimized GT gene sbmGT1, which was designed based on BmmGT1, was heterologously expressed in the piericidin producer Streptomyces youssoufiensis OUC6819. Piericidin glycosides thus significantly accumulated, leading to the identification of four new glucopiericidins (compounds 3, 4, 6, and 7). Furthermore

SUBMITTER: Liu Z 

PROVIDER: S-EPMC8315951 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature