Molecular Mechanism by which Prominent Human Gut Bacteroidetes Utilize Mixed-Linkage Beta-Glucans, Major Health-Promoting Cereal Polysaccharides
Kazune Tamura,
Glyn R. Hemsworth,
Guillaume Déjean,
Theresa E. Rogers,
Nicholas A. Pudlo,
Karthik Urs,
Namrata Jain,
Gideon J. Davies,
Eric C. Martens,
Harry Brumer
Affiliations
Kazune Tamura
Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
Glyn R. Hemsworth
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Guillaume Déjean
Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada
Theresa E. Rogers
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Nicholas A. Pudlo
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Karthik Urs
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Namrata Jain
Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
Gideon J. Davies
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Eric C. Martens
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Harry Brumer
Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada; Department of Botany, University of British Columbia, 3200 University Boulevard, Vancouver, BC V6T 1Z4, Canada; Corresponding author
Summary: Microbial utilization of complex polysaccharides is a major driving force in shaping the composition of the human gut microbiota. There is a growing appreciation that finely tuned polysaccharide utilization loci enable ubiquitous gut Bacteroidetes to thrive on the plethora of complex polysaccharides that constitute “dietary fiber.” Mixed-linkage β(1,3)/β(1,4)-glucans (MLGs) are a key family of plant cell wall polysaccharides with recognized health benefits but whose mechanism of utilization has remained unclear. Here, we provide molecular insight into the function of an archetypal MLG utilization locus (MLGUL) through a combination of biochemistry, enzymology, structural biology, and microbiology. Comparative genomics coupled with growth studies demonstrated further that syntenic MLGULs serve as genetic markers for MLG catabolism across commensal gut bacteria. In turn, we surveyed human gut metagenomes to reveal that MLGULs are ubiquitous in human populations globally, which underscores the importance of gut microbial metabolism of MLG as a common cereal polysaccharide. : Mixed-linkage β(1,3)/β(1,4)-glucan (MLG) is an important complex dietary polysaccharide (dietary fiber), the degradation of which in the human gut depends on the resident microbiota. Tamura et al. outline the molecular mechanism of MLG utilization by Bacteroides ovatus and reveal that the majority of surveyed humans possess MLG-utilizing Bacteroidetes. Keywords: microbiota, dietary fiber, complex carbohydrates, polysaccharide, polysaccharide utilization locus, Bacteroidetes, mixed-linkage glucan, barley beta-glucan, oat beta-glucan, carbohydrate-active enzymes
