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Complex N-glycan breakdown by gut Bacteroides involves an extensive enzymatic apparatus encoded by multiple co-regulated genetic loci

DOI: 10.1038/s41564-019-0466-x DOI Help

Authors: Justina Briliūtė (Newcastle University) , Paulina A. Urbanowicz (Ludger Ltd) , Ana S. Luis (University of Michigan Medical School) , Arnaud Basle (Newcastle University) , Neil Paterson (Diamond Light Source) , Osmond Rebello (Ludger Ltd) , Jenifer Hendel (Ludger Ltd) , Didier A. Ndeh (Newcastle University) , Elisabeth C. Lowe (Newcastle University) , Eric C. Martens (University of Michigan Medical School) , Daniel I. R. Spencer (Ludger Ltd) , David N. Bolam (Newcastle University) , Lucy I. Crouch (Newcastle University)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Microbiology , VOL 39

State: Published (Approved)
Published: June 2019
Diamond Proposal Number(s): 13587 , 18598

Abstract: Glycans are the major carbon sources available to the human colonic microbiota. Numerous N-glycosylated proteins are found in the human gut, from both dietary and host sources, including immunoglobulins such as IgA that are secreted into the intestine at high levels. Here, we show that many mutualistic gut Bacteroides spp. have the capacity to utilize complex N-glycans (CNGs) as nutrients, including those from immunoglobulins. Detailed mechanistic studies using transcriptomic, biochemical, structural and genetic techniques reveal the pathway employed by Bacteroides thetaiotaomicron (Bt) for CNG degradation. The breakdown process involves an extensive enzymatic apparatus encoded by multiple non-adjacent loci and comprises 19 different carbohydrate-active enzymes from different families, including a CNG-specific endo-glycosidase activity. Furthermore, CNG degradation involves the activity of carbohydrate-active enzymes that have previously been implicated in the degradation of other classes of glycan. This complex and diverse apparatus provides Bt with the capacity to access the myriad different structural variants of CNGs likely to be found in the intestinal niche.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)