Identification and characterization of glycosyltransferases catalyzing direct xanthone 4-C-glycosylation in Hypericum perforatum

Xanthones are compounds with a diphenyl ether skeleton mainly found in plants and often glycosylated at carbon atoms. Although many C-glycosyltransferases (CGTs) participating in flavone C-glycosylation have been identified, MiCGT from Mangifera indica, adding sugar to an open-chain benzophenone skeleton, is the only identified xanthone biosynthesis-related CGT. Here, we identified two CGTs from Hypericum perforatum that add sugar to the closed-ring xanthone, but not benzophenone. These CGTs catalyze sugar transfer to the C-4 position of norathyriol (1,3,6,7-tetrahydroxyxanthone) to form isomangiferin (1,3,6,7-tetrahydroxyxanthone 4-C-glucoside), a major xanthone C-glucoside. This is the first study to report CGTs that mediate the direct C-glycosylation of xanthone.