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来自嗜黏蛋白阿克曼氏菌的碳水化合物活性酶可将黏蛋白O-聚糖完全分解。

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

作者信息

Bakshani Cassie R, Ojuri Taiwo O, Pilgaard Bo, Holck Jesper, McInnes Ross, Kozak Radoslaw P, Zakhour Maria, Çakaj Sara, Kerouedan Manon, Newton Emily, Bolam David N, Crouch Lucy I

机构信息

Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.

Protein Chemistry and Enzyme Technology Section, DTU Bioengineering, Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.

出版信息

Nat Microbiol. 2025 Feb;10(2):585-598. doi: 10.1038/s41564-024-01911-7. Epub 2025 Jan 31.

DOI:10.1038/s41564-024-01911-7
PMID:39891011
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11790493/
Abstract

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.

摘要

嗜黏蛋白阿克曼氏菌是一种存在于大肠黏膜层的人类微生物共生体。其主要碳源是高度异质的黏蛋白糖蛋白,它利用一系列碳水化合物活性酶和硫酸酯酶来获取这种复杂的能量来源。在此,我们描述了嗜黏蛋白阿克曼氏菌中54种糖苷水解酶、11种硫酸酯酶和1种多糖裂解酶的生化特性,以全面了解它们的碳水化合物降解活性。这是通过使用各种液相色谱技术、质谱、酶动力学和薄层色谱实现的。这些结果得到了嗜黏蛋白阿克曼氏菌生长和全细胞分析的支持。我们发现这些酶可以协同作用,将黏蛋白多肽上的O-聚糖完全降解,直至核心N-乙酰半乳糖胺。此外,这些酶可以分解人乳寡糖、神经节苷脂和球蛋白聚糖结构,显示出它们靶向多种宿主聚糖的能力。这些数据为了解肠道微生物群成员嗜黏蛋白阿克曼氏菌的完整降解能力提供了资源。

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and synergistically protect from colitis by promoting ILC3 in the gut.
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