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PreprintCited by 15Gut microbiota and healthFood composition and propertiesEnzyme Production and Characterization

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Spatial constraints drive amylosome-mediated resistant starch degradation by Ruminococcus bromii in the human colon

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Wimmer, Benedikt H, Moraïs, Sarah, Amit, Itai, Tovar-Herrera, Omar, Tatli, Meltem, Trautwein-Schult, Anke, Tödtli, Paloma, Simoni, Sebastian, Lisibach, Matteo, Levin, Liron, Becher, Dörte, Bayer, Edward A., Medalia, Ohad, Mizrahi, Itzhak·2025·Nature Communications
DOI 10.1101/2025.03.31.646359PMC PMC12663171

Preprint — published as 10.1038/s41467-025-65800-1 · Paper page

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Abstract

Degradation of complex dietary fiber by gut microbes is essential for colonic fermentation, short-chain fatty acid production, and microbiome function. Ruminococcus bromii is the primary resistant starch (RS) degrader in humans, which relies on the amylosome, a specialized cell-bound enzymatic complex. To unravel its architecture, function, and the interplay among its components, we applied an holistic multilayered approach and found that amylosome composition RS degradation, and enzymatic synergy are regulated at two levels: structural constraints enforcing enzyme proximity and expression-driven shifts in enzyme proportions. Cryo-electron tomography revealed that the amylosome comprises a constitutive extracellular layer extending toward the RS. However, proteomics demonstrated its remodeling across different growth conditions, with Amy4 and Amy16 comprising 60% of the amylosome in response to RS. Structural and biochemical analyses revealed complementarity and synergistic RS degradation by these enzymes, which allow R. bromii to fine-tune its adaptation to dietary fiber and shape colonic metabolism.

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Metadata

Authors
Wimmer, B. H., Moraïs, S., Amit, I., Tovar-Herrera, O., Tatli, M., Trautwein-Schult, A., Tödtli, P., Simoni, S., Lisibach, M., Levin, L., Becher, D., Bayer, E. A., Medalia, O., & Mizrahi, I.
Affiliations
  • University of Zurich (CH)
  • Ben-Gurion University of the Negev (IL)
  • Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland
  • Institute of Microbiology, Department of Microbial Proteomics, University of Greifswald, 17489 Greifswald, Germany
  • Universität Greifswald (DE)
Corresponding author
  • Medalia, Ohad
  • Mizrahi, Itzhak
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2025-03-31
Volume
16
Issue
1
Pages
10763-10763
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2025.03.31.646359
PMC
PMC12663171
OpenAlex
W4416719927
Cited by
15
References
2
Citations by year
2026: 14 · 2025: 1
FWCI
4.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation
  • Novartis Foundation
  • University of Aberdeen
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (227822, 10000885)
  • Israel Science Foundation
  • Novartis Stiftung für Medizinisch-Biologische Forschung
  • Universität Zürich
  • Universität Greifswald
  • H2020 European Research Council (866530)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Food composition and properties
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
Keywords
Ruminococcus bromii, dietary fiber, colonic fermentation, gut microbiota, enzyme complex assembly, cryo-electron tomography, extracellular matrix, short-chain fatty acids, human colon
MeSH terms
Gastrointestinal Microbiome, Bacterial Proteins, Colon, Dietary Fiber, Humans, Starch, Cryoelectron Microscopy, Proteomics, Ruminococcus

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