An Efficient Strategy for the Glycosylation of Total Bufadienolides in Venenum Bufonis

Drug discovery process and biological research critically depend on the access to libraries of molecules with interesting biomolecular properties. Thus, it is extremely important to develop robust and efficient strategies to access structurally diverse druglike compound collections. We introduce here a strategy for glycosylation of the total bufadienolides in Venenum Bufonis (VB) by using a permissive glycosyltransferase YjiC1 with conversion rates up to 90%, which was more efficient than other two enzymes. Compared to the crude extract, the glycosylated VB showed lower toxicity against zebrafish and more potent inhibitory activity on Na+,K+-ATPase. The results demonstrated the great advantages of using permissive enzymes as an alternative strategy for producing structurally diverse natural product-like libraries.