Biocatalytic C-Glucosylation of Coumarins Using an Engineered C-Glycosyltransferase

The enzymatic synthesis of coumarin C-glucosides by an engineered C-glycosyltransferase, MiCGTb–GAGM, was explored in vitro and in vivo. MiCGTb–GAGM exhibited a robust C-glucosylation capability toward structurally diverse coumarin derivatives. The whole-cell bioconversion of MiCGTb–GAGM was exploited for large-scale production of coumarin C-glucosides. Two C-glucosides exhibited potent SGLT2 inhibitory activities with IC50 values at 10–6 M. These findings provide cost-effective and practical synthetic strategies to generate structurally diverse and novel bioactive coumarin C-glycosides for drug discovery.