Metabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus

DOI: 10.1038/s41467-020-14509-4

Authors: Didier Ndeh (Newcastle University; Quadram Institute Bioscience) , Arnaud Basle (Newcastle University) , Henrik Strahl (Newcastle University) , Edwin A. Yates (University of Liverpool) , Urszula L. Mcclurgg (University of Liverpool) , Bernard Henrissat (CNRS, Aix-Marseille University; Institut National de la Recherche Agronomique; King Abdulaziz University) , Nicolas Terrapon (CNRS, Aix-Marseille University; Institut National de la Recherche Agronomique) , Alan Cartmell (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 18598

Abstract: The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the ‘sulfation problem’ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.

Journal Keywords: Glycobiology; Microbiome; Polysaccharides; X-ray crystallography

Diamond Keywords: Gut Microbiota; Bacteria

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I24-Microfocus Macromolecular Crystallography

Added On: 06/02/2020 14:04

Documents:
s41467-020-14509-4.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Genetics Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)