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

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 A. muciniphila uses an array of Carbohydrate-active enzymes and sulfatases to access this complex energy source. Here we describe the biochemical characterisation of fifty-four glycoside hydrolases, eleven sulfatases, and one polysaccharide lyase from A. muciniphila to provide a holistic understanding of the carbohydrate-degrading activities. The results provide an extensive insight into the sequence of O-glycan degradation and how A. muciniphila can access this structurally variable substrate. One of the most outstanding elements of this work was the demonstration that these enzymes can act synergistically to degrade the O-glycans on the mucin polypeptide to completion, down to the core GalNAc. Additionally, human breast milk oligosaccharide, ganglioside, and globoside glycan structures were included in the study to understand the full degradative capability of A. muciniphila.