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.

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BibTeX RIS

BibTeX

@article{liu2026cleavage,
  title = {{Cleavage of xanthone and flavone C–glycosidic bonds by the enzyme complex LaGME from gut Lachnospiraceae}},
  author = {Wancang Liu and Xiaoyu Tao and Shuai Fan and Xiayun Li and Zexin Liu and Hongyan Zhang and Jun Li and Wenni He and Dewu Zhang and Tao Zhang and Tao Zhang and Xu Pang and Zhaoyong Yang and Baiping Ma and Haibo Xiang and Liyan Yu},
  journal = {Communications Biology},
  year = {2026},
  month = oct,
  doi = {10.1038/s42003-026-10896-4},
  url = {https://www.nature.com/articles/s42003-026-10896-4},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Cleavage of xanthone and flavone C–glycosidic bonds by the enzyme complex LaGME from gut Lachnospiraceae
AU  - Wancang Liu
AU  - Xiaoyu Tao
AU  - Shuai Fan
AU  - Xiayun Li
AU  - Zexin Liu
AU  - Hongyan Zhang
AU  - Jun Li
AU  - Wenni He
AU  - Dewu Zhang
AU  - Tao Zhang
AU  - Tao Zhang
AU  - Xu Pang
AU  - Zhaoyong Yang
AU  - Baiping Ma
AU  - Haibo Xiang
AU  - Liyan Yu
PY  - 2026
DA  - 2026/10/30
JO  - Communications Biology
DO  - 10.1038/s42003-026-10896-4
UR  - https://www.nature.com/articles/s42003-026-10896-4
AB  - 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.
SN  - 2399-3642
ER  -

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