Toggle Main Menu Toggle Search

Open Access padlockePrints

Carbohydrate-active enzymes from Akkermansia muciniphila break down mucin O-glycans to completion

Lookup NU author(s): Cassie Bakshani, Maria Zakhour, Dr David BolamORCiD, Dr Lucy Crouch

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2025. Akkermansia muciniphila is a human microbial symbiont residing in the mucosal layer of the large intestine. Its main carbon source is the highly heterogeneous mucin glycoprotein, and it uses an array of carbohydrate-active enzymes and sulfatases to access this complex energy source. Here we describe the biochemical characterization of 54 glycoside hydrolases, 11 sulfatases and 1 polysaccharide lyase from A. muciniphila to provide a holistic understanding of their carbohydrate-degrading activities. This was achieved using a variety of liquid chromatography techniques, mass spectrometry, enzyme kinetics and thin-layer chromatography. These results are supported with A. muciniphila growth and whole-cell assays. We find that these enzymes can act synergistically to degrade the O-glycans on the mucin polypeptide to completion, down to the core N-acetylgalactosaime. In addition, these enzymes can break down human breast milk oligosaccharide, ganglioside and globoside glycan structures, showing their capacity to target a variety of host glycans. These data provide a resource to understand the full degradative capability of the gut microbiome member A. muciniphila.


Publication metadata

Author(s): Bakshani CR, Ojuri TO, Pilgaard B, Holck J, McInnes R, Kozak RP, Zakhour M, Cakaj S, Kerouedan M, Newton E, Bolam DN, Crouch LI

Publication type: Article

Publication status: Published

Journal: Nature Microbiology

Year: 2025

Volume: 10

Pages: 585-598

Online publication date: 31/01/2025

Acceptance date: 10/12/2024

Date deposited: 18/02/2025

ISSN (electronic): 2058-5276

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41564-024-01911-7

DOI: 10.1038/s41564-024-01911-7

Data Access Statement: The full RNA-seq data are provided in Supplementary Data 1 and submitted to https://www.ebi.ac.uk/ena/browser/home with accession number PRJEB76658. Source data are provided with this paper.


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
Academy of Medical Sciences (SBF0061175)
BBSRC Midlands Integrative Biosciences Training Partnership (MIBTP)
BB/M029018/1Biotechnology and Biological Sciences Research Council (BBSRC)
Department of Biotechnology and Biomedicine, Section for Protein Chemistry and Technology, Technical University of Denmark
Ludger (Oxford, UK)
Wellcome Trust and Royal Society (224240/Z/21/Z)

Share