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

Abstract

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.

Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica

“…Since the first experimental validation of a CGT (OsCGT, UGT72B1 ) in Oryza sativa ssp. indica, numerous key CGTs involved in the synthesis of C- glycosyl flavonoids, xanthone C- glycosides, and coumarin C- glycosides have been verified in plants ( Brazier-Hicks et al., 2009 ; Wang et al., 2020 ; Chen et al., 2021 ; Uchida et al., 2021 ). The formation process of these C- glycosides can be roughly divided into two steps.…”

“…In Mangifera indica , MiCGT transfers UDP-glucose to maclurin to generate 3- C- glucosylmaclurin, which is subsequently cyclized by xanthone synthase to produce mangiferin ( Chen et al., 2015 ; Chong et al., 2022 ). In contrast, in Hypericum perforatum , the xanthone skeleton is directly C- glycosylated to form C- glycoside xanthone, and N4CGT1 and N4CGT2 directly catalyze the C- 4 glycosylation of norathyriol to form isomangiferin ( Uchida et al., 2021 ). In Morus alba and Angelica decursiva , MaCGT and AbCGT , respectively, are involved in C- glycoside coumarin biosynthesis ( Chen et al., 2021 ; Wang et al., 2022 ).…”