Abstract
The thick mucus layer of the gut provides a barrier to infiltration of the underlying epithelia by both the normal microbiota and enteric pathogens. Some members of the microbiota utilise mucin glycoproteins as a nutrient source, but a detailed understanding of the mechanisms used to breakdown these complex macromolecules is lacking. Here we describe the discovery and characterisation of endo-acting enzymes from prominent mucin-degrading bacteria that target the polyLacNAc structures within oligosaccharide side chains of both animal and human mucins. These O-glycanases are part of the large and diverse glycoside hydrolase 16 (GH16) family and are often lipoproteins, indicating that they are surface located and thus likely involved in the initial step in mucin breakdown. These data provide a significant advance in our knowledge of the mechanism of mucin breakdown by the normal microbiota. Furthermore, we also demonstrate the potential use of these enzymes as tools to explore changes in O-glycan structure in a number of intestinal disease states.
Original language | English |
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Article number | 4017 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 11 Aug 2020 |
Bibliographical note
Funding Information: We thank Carl Morland (Newcastle University, UK) for his expert technical assistance. We thank Dr. Mirjam Czjzek for her expert advice on the structural data and Prof Robert Hirt for his insightful conversations about phylogenetics. We would like to thank Diamond Light Source (Oxfordshire, UK) for beamtime (proposal mx18598) and staff of beamline I03, I04-1 and I24. We are grateful to Newcastle Biobank and NIHR Newcastle Biomedical Research Centre. Dr. Jose Muñoz-Muñoz kingly gifted the arabinogalactan substrates used. The NEC samples were collected as part of the ethically approved SERVIS study (REC 10/H0908/39). The colorectal cancer cell lines were from the Department of Surgery, Leiden University Medical Centre (LUMC), Leiden. The work was funded by a BBSRC/Innovate UK IB catalyst award ‘Glycoenzymes for Bioindustries’ (BB/M029018/1).Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
Keywords
- Animals
- Bacteria/classification
- Crystallography, X-Ray
- Gastrointestinal Microbiome
- Glycoside Hydrolases/genetics
- Hexosaminidases/chemistry
- Humans
- Membrane Glycoproteins/chemistry
- Molecular Structure
- Mucins/chemistry
- Phylogeny
- Polysaccharides/chemistry
- Structure-Activity Relationship
- Substrate Specificity
ASJC Scopus subject areas
- General Physics and Astronomy
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology