Docking-guided rational engineering of a macrolide glycosyltransferase glycodiversifies epothilone B.

ABSTRACT: Glycosyltransferases typically display acceptor substrate flexibility but more stringent donor specificity. BsGT-1 is a highly effective glycosyltransferase to glycosylate macrolides, including epothilones, promising antitumor compounds. Here, we show that BsGT-1 has three major regions significantly influencing the glycodiversification of epothilone B based on structural molecular docking, "hot spots" alanine scanning, and site saturation mutagenesis. Mutations in the PSPG-like motif region and the C2 loop region are more likely to expand donor preference; mutations of the flexible N3 loop region located at the mouth of the substrate-binding cavity produce novel epothilone oligosaccharides. These "hot spots" also functioned in homologues of BsGT-1. The glycosides showed significantly enha

SUBMITTER: Zhang P 

PROVIDER: S-EPMC8795383 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature