Ndeh, Didier, Munoz, Jose Munoz, Cartmell, Alan 
ORCID: 0000-0002-5512-249X, Bulmer, David, Wills, Corinne, Henrissat, Bernard and Gray, Joseph
(2018)
The human gut microbe <i>Bacteroides thetaiotaomicron</i> encodes the founding member of a novel glycosaminoglycan-degrading polysaccharide lyase family PL29.
JOURNAL OF BIOLOGICAL CHEMISTRY, 293 (46).
pp. 17906-17916.
Abstract
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 <i>Bacteroides thetaiotaomicron.</i> 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 <i>B. thetaiotaomicron</i> NMR and UV spectroscopic assays revealed that it encodes a novel polysaccharide lyase (PL), hereafter referred to as BtCDH, reflecting its source (<i>B. thetaiotaomicron</i> (<u>Bt</u>)) and its ability to degrade the GAGs <u>C</u>S, dermatan sulfate (<u>D</u>S), and hyaluronic acid (<u>H</u>A). When incubated with HA, BtCDH generated a series of unsaturated HA sugars, including Δ<sup>4,5</sup>UA-GlcNAc, Δ<sup>4,5</sup>UA-GlcNAc-GlcA-GlcNac, Δ<sup>4,5</sup>UA-[GlcNAc-GlcA]<sub>2</sub>-GlcNac, and Δ<sup>4,5</sup>UA-[GlcNAc-GlcA]<sub>3</sub>-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 <i>B. thetaiotaomicron</i> 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | chondroitin sulfate, hyaluronan, hyaluronate lyase, carbohydrate metabolism, bacterial metabolism, polysaccharide, CAZymes, cell surface enzyme, glycosaminoglycan degradation, human gut microbiota, PL29 |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Sep 2019 15:52 |
| Last Modified: | 05 Oct 2023 18:57 |
| DOI: | 10.1074/jbc.RA118.004510 |
| Open Access URL: | http://www.jbc.org/content/early/2018/09/27/jbc.RA... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3054142 |
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