A family of di-glutamate mucin-degrading enzymes that bridges glycan hydrolases and peptidases

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Microbes utilize polysaccharides to protect their surfaces and build biofilms, whereas metazoans employ large mucins densely decorated with O-glycans to protect surfaces and keep microbes at a distance. However, gut microbes in mucus also feed on host mucins, thus imposing a need for continuous renewal to maintain protection, clearance and mucus homeostasis. Glycopeptidases that can cleave mucins are known, but mucinases that specifically cleave mucins are not. Here we report the discovery of such microbial mucinases that cleave mucins with trimmed glycans, recognize dense clusters of O-glycans, and employ a structural fold and catalytic machinery reminiscent of glycan hydrolases and peptidases. These di-glutamate mucinases are also found in eukaryotes, and we propose that they are designed to clear mucins following scavenging of O-glycans to promote healthy gut–microbiome homeostasis.
OriginalsprogEngelsk
TidsskriftNature Catalysis
Vol/bind7
Sider (fra-til)386–400
Antal sider15
ISSN2520-1158
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
This work was supported by the Novo Nordisk Foundation (NNF22OC0076899 to H.J.J., NNF20SA0067193 to B.H. and NNF210071658 to H.C.), the Danish National Research Foundation (DNRF107), the Lundbeck Foundation, the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 787684 (to C.B.), the Spanish Ministry of Science, Innovation and Universities (BFU2016-75633-P, PID2019-105451GB-100, PID2022-136362NB-100, PID2021-127622OB-100, PID2020-118893GB-100 and CEX2021-001202-M), Gobierno de Aragón (E34_R17 and LMP58_18) with FEDER (2014–2020) funds for ‘Building Europe from Aragón’ for financial support (to R.H.-G.), and the Agency for Management of University and Research Grants of Catalonia (AGAUR, 2021-SGR-00680 to C.R.). We thank ALBA (Barcelona, Spain) synchrotron beamline XALOC, and Red Española de Supercomputación (RES-BSC) for computer time in CTE-Power and MareNostrum IV. Q.L. thanks the EU for a Marie-Skłodowska Curie fellowship (MCSA-IF-2020, agreement no. 101025071). R.H.-G. thanks M. del Carmen Hurtado-Lago for help with the design of Fig. .

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2024.

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