Exploiting the aglycon promiscuity of glycosyltransferase Bs-YjiC from Bacillus subtilis and its application in synthesis of glycosides

•Glycosyltransferase Bs-YjiC from B. subtilis 168 was expressed in E. coli.•Bs-YjiC showed aglycon promiscuity toward 19 structurally diverse compounds.•Twenty-four glycosylated products of 17 aglycons were purified from scale-up reactions.•Bs-YjiC could catalyse the formation of O-, N-, and S-linkage glycosides.•Bs-YjiC coupled to sucrose synthase was a powerful approach for glycosylation.

Glycosylation is a prominent biological mechanism for structural and functional diversity of natural products. Uridine diphosphate-dependent glycosyltransferases with aglycon promiscuity are generally recognised as effective biocatalysts for glycodiversification of natural products for practical applications. In this study, the aglycon promiscuity of glycosyltransferase Bs-YjiC from Bacillus subtilis 168 was explored. Bs-YjiC, with uridine diphosphate glucose (UDPG) as sugar donor, exhibited robust capabilities to glycosylate 19 structurally diverse types of drug-like scaffolds with regio- and stereospecificities and form O-, N- and S-linkage glycosides. Twenty-four glycosides of 17 aglycons were purified from scale-up reactions using Bs-YjiC as a biocatalyst, and their structures were confirmed by nuclear magnetic resonance spectra. Furthermore, a one-pot reaction by coupling Bs-YjiC to sucrose synthase from Arabidopsis thaliana was applied to glycosylate pterostilbene. Without adding the costly UDPG as sugar donor, 9 mM (3.8 g/L) pterostilbene 4′-O-β-glucoside was obtained by periodic feeding of pterostilbene. These results suggest the aglycon promiscuity of Bs-YjiC and demonstrate its significant application prospect in biosynthesis of valuable natural products.