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Lookup NU author(s): Dr Didier Ndeh, Dr Jose Munoz Munoz, Dr Alan Cartmell, Dr David Bulmer, Dr Corinne Wills
This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society for Biochemistry and Molecular Biology Inc., 2018.
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© 2018 Ndeh et al. Glycosaminoglycans (GAGs) and GAG-degrading enzymes have wide-ranging applications in the medical and biotechnological industries. The former are also an important nutrient source for select species of the human gut microbiota (HGM), a key player in host–microbial interactions. How GAGs are metabolized by the HGM is therefore of interest and has been extensively investigated in the model human gut microbe Bacteroides thetaiotaomicron. The presence of as-yet uncharacterized GAG-inducible genes in its genome and of related species, however, is testament to our incomplete understanding of this process. Nevertheless, it presents a potential opportunity for the discovery of additional GAG-degrading enzymes. Here, we investigated a gene of unknown function (BT_3328) from the chondroitin sulfate (CS) utilization locus of B. thetaiotaomicron. NMR and UV spectroscopic assays revealed that it encodes a novel polysaccharide lyase (PL), hereafter referred to as BtCDH, reflecting its source (B. thetaiotaomicron (Bt)) and its ability to degrade the GAGs CS, dermatan sulfate (DS), and hyaluronic acid (HA). When incubated with HA, BtCDH generated a series of unsaturated HA sugars, including4,5UA-GlcNAc,4,5UA-GlcNAc-GlcA-GlcNac,4,5UA-[GlcNAc-GlcA]2-GlcNac, and4,5UA-[GlcNAc-GlcA]3-GlcNac, as end products and hence was classed as endo-acting. A combination of genetic and biochemical assays revealed that BtCDH localizes to the cell surface of B. thetaiotaomicron where it enables extracellular GAG degradation. BtCDH homologs were also detected in several other HGM species, and we therefore propose that it represents the founding member of a new polysaccharide lyase family (PL29). The current discovery also contributes new insights into CS metabolism by the HGM.
Author(s): Ndeh D, Munoz JM, Cartmell A, Bulmer D, Wills C, Henrissat B, Gray J
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Year: 2018
Volume: 293
Issue: 46
Pages: 17906-17916
Print publication date: 16/11/2018
Online publication date: 27/09/2018
Acceptance date: 24/09/2018
Date deposited: 17/12/2018
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology Inc.
URL: https://doi.org/10.1074/jbc.RA118.004510
DOI: 10.1074/jbc.RA118.004510
PubMed id: 30262663
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