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Research Themes Protein design

Novel Proteins and Networks: Polysaccharide Metabolism in the Human Gut

SBKB [doi:10.1038/sbkb.2014.198]
Featured Article - May 2014
Short description: Comparative genomics identifies new components and regulatory networks for the utilization of complex carbohydrates by Bacteroides thetaiotaomicron.

Comparative genomics inference of DNA-binding sites and regulons controlling carbohydrate utilization pathways in Bacteroides spp. Figure courtesy of Dmitry Rodionov.

The maintenance of a diverse community of microbes within the human digestive system is important for health. The gut microbiota contributes several metabolic pathways key to the digestion of certain nutrients, including polysaccharides such as starch, hemicellulose and pectin. Bacteroides is the most abundant genus in the human digestive tract, and B. thetaiotaomicron its most studied species. Although most members of the gut microbiome can process a single type of polysaccharide, B. thetaiotaomicron is a generalist, able to metabolize a wide variety of polysaccharide substrates.

Most proteins required for the breakdown of polysaccharides participate in transport and enzymatic processing of carbohydrates, or in the transcriptional regulation of those factors. To further define the pathways involved in polysaccharide processing by bacterial symbionts, Rodionov and colleagues (PSI JCSG) have undertaken a comparative genomic analysis of the carbohydrate utilization regulatory networks of 11 Bacteroides species. The authors focused on two key regulatory systems involved in the transcriptional regulation of polysaccharide utilization loci (PUL): SusR-like regulators and hybrid two-component systems (HTCSs). Each type of regulator is membrane-anchored and contains a sugar sensor domain and a DNA-binding domain that controls the trancription of different PUL.

In order to predict the function of HTCSs and SusR-like regulators, the authors first looked for genes involved in glycolytic pathways that co-localize with the same regulator across several Bacteroides species. In turn, the function of the genes associated with each regulator could be used to predict the sugar-binding specificity of its sensor domain. Similarly, the DNA-binding specificity of some regulators could be predicted from the comparison of regions upstream of genes that are co-regulated across species. By combining the results of these analyses, the authors inferred a number of previously uncharacterized metabolic and regulatory pathways.

Overall, the study added 173 novel genes (coding for 82 enzymes, 22 transporters, 32 transcription factors and 37 proteins of unknown functions) to our knowledge of the metabolic network of B. thetaiotaomicron. This work also predicts sugar-binding specificities for several HTCS and SusR-like regulator sensor domains. This information should be useful in guiding future structural analyses of sugar-binding proteins.

Stéphane Larochelle

References

  1. D.A. Ravcheev et al. Polysaccharides utilization in human gut bacterium Bacteroides thetaiotaomicron: comparative genomics reconstruction of metabolic and regulatory networks.
    BMC Genomics. 14, 873 (2013). doi:10.1186/1471-2164-14-873

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