Cleavage of xanthone and flavone C–glycosidic bonds by the enzyme complex LaGME from gut Lachnospiraceae

Abstract Aglycones, the bioactive metabolites of C– glycosides, can be obtained through the deglycosylation of naturally abundant C– glycosides. However, C– glycosides are more resistant to enzymatic and chemical degradation. Gut microbiota and its enzymes are known to cleave the C–C glycosidic bond, but only a limited number of active strains and functional enzymes have been identified. Here we show that a new C– deglycosylation gene cluster encoding the g lycoside- m etabolizing e nzyme from La chnospiraceae (LaGME), an enzyme complex consisting of a C – g lycoside o xidoreductase (LaCGO1) and a C – g lycoside e limination enzyme complex (LaCGE), was discovered using the DUF6379 domain-containing protein as a probe. LaGME demonstrates significant activities toward xanthone-type and flavone-type C– glycosides. After investigation into heterologous expression, structural determination and catalytic mechanism, a LaGME-mediated one-pot cascade enzymatic reaction system was developed for green production of aglycones. This research provides an approach to uncover C– glycoside-metabolizing enzymes in nature, as well as a preliminary basis for the sustainable production of value-added bioactive aglycones from glycosides.