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

TY - JOUR

T1 - Metabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus

AU - Ndeh, Didier

AU - Baslé, Arnaud

AU - Strahl, Henrik

AU - Yates, Edwin A.

AU - McClurgg, Urszula L.

AU - Henrissat, Bernard

AU - Terrapon, Nicolas

AU - Cartmell, Alan

N1 - Funding Information: The authors would like to thank Diamond Light Source for beamtime and the staff of beamlines I04 and I24 for assistance with crystal testing and collection. We would also like to thank Prof. Eduardo Groisman and Dr Guy Townsend for providing B. theta strains. We would also like to thank Carl Morland for his expert technical assistance. This work was supported by start up funds provided by Liverpool University to A.C. The work was also supported by the MRC CiC award MC_PC_17166 held by E.A.Y and a Wellcome ISSF grant 204822/Z/16/Z awarded to U.L.M. A.B. was supported on an ERC advanced award (Grant 322820). Publisher Copyright: © 2020, The Author(s).

PY - 2020/1/31

Y1 - 2020/1/31

N2 - 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.

AB - 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.

KW - Glycobiology

KW - Microbiome

KW - Polysaccharides

KW - X-ray crystallography

UR - https://www.scopus.com/pages/publications/85078826440

U2 - 10.1038/s41467-020-14509-4

DO - 10.1038/s41467-020-14509-4

M3 - Article

C2 - 32005816

AN - SCOPUS:85078826440

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 646

ER -