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Carbohydrate-active enzymes (CAZymes) in the gut microbiome

Abstract

The 1013–1014 microorganisms present in the human gut (collectively known as the human gut microbiota) dedicate substantial percentages of their genomes to the degradation and uptake of carbohydrates, indicating the importance of this class of molecules. Carbohydrates function not only as a carbon source for these bacteria but also as a means of attachment to the host, and a barrier to infection of the host. In this Review, we focus on the diversity of carbohydrate-active enzymes (CAZymes), how gut microorganisms use them for carbohydrate degradation, the different chemical mechanisms of these CAZymes and the roles that these microorganisms and their CAZymes have in human health and disease. We also highlight examples of how enzymes from this treasure trove have been used in manipulation of the microbiota for improved health and treatment of disease, in remodelling the glycans on biopharmaceuticals and in the potential production of universal O-type donor blood.

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Fig. 1: Overview of the CAZyme classes and associated modules.
Fig. 2: Mechanism of α-mannan digestion by B. thetaiotaomicron.
Fig. 3: Host glycan degradation by Bacteroidetes.
Fig. 4: Glucuronidation of small molecules and reactivation by bacterial GUSs.
Fig. 5: Applications of enzymes from the gut microbiome.

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Acknowledgements

The authors were supported by funding from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC) during the writing of this Review.

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Correspondence to Stephen G. Withers.

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P.R. and S.G.W. are co-founders of a company to develop enzymes for conversion of blood type. The research underlying that is mentioned in this Review. J.F.W. and R.K.B. declare no competing interests.

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Related links

CAZy database: http://www.cazy.org/

CAZypedia: https://www.cazypedia.org

Glossary

Short-chain fatty acids

Fatty acids containing up to six carbon atoms (predominantly acetate, propionate and butyrate in the human gut) that can be produced by gut microorganisms during fermentation.

Cross-feeding

A phenomenon in which microorganisms utilize metabolites and degradation products derived from other microorganisms.

Outer membrane vesicles

Vesicles with distinct protein cargo that are derived from the outer membrane of Gram-negative bacteria and are released into the environment.

E1cb mechanism

A two-step chemical reaction in which an acidic proton is abstracted by a base to form a stabilized carbanion, followed by elimination of a leaving group as the carbanion lone pair moves to form a π-bond with the adjacent atoms.

Xenobiotics

Molecules that are not produced or expected to be found within an organism (for example, drugs).

Endobiotics

Molecules that are produced or are expected to be found within an organism (for example, hormones).

Antibody-dependent cellular toxicity

An immune response in which binding of antibodies to a cell surface results in the lysis of that cell by effector cells of the immune system.

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Wardman, J.F., Bains, R.K., Rahfeld, P. et al. Carbohydrate-active enzymes (CAZymes) in the gut microbiome. Nat Rev Microbiol (2022). https://doi.org/10.1038/s41579-022-00712-1

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