Overflow metabolism in Escherichia coli results from efficient proteome allocation
Open accessAbstract
Overflow metabolism refers to the seemingly wasteful strategy in which cells use fermentation instead of the more efficient respiration to generate energy, despite the availability of oxygen. Known as the Warburg effect in the context of cancer growth, this phenomenon occurs ubiquitously for fast-growing cells, including bacteria, fungi and mammalian cells, but its origin has remained unclear despite decades of research. Here we study metabolic overflow in Escherichia coli, and show that it is a global physiological response used to cope with changing proteomic demands of energy biogenesis and biomass synthesis under different growth conditions. A simple model of proteomic resource allocation can quantitatively account for all of the observed behaviours, and accurately predict responses to new perturbations. The key hypothesis of the model, that the proteome cost of energy biogenesis by respiration exceeds that by fermentation, is quantitatively confirmed by direct measurement of protein abundances via quantitative mass spectrometry.
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The results reinforce the idea that there is a simple principle for protein allocation in microorganisms.
“These results reinforce the idea that there is a simple principle for protein allocation in microorganisms (Basan et al, 2015; Hui et al, 2015; Nilsson & Nielsen, 2016).”
From Improving the phenotype predictions of a yeast genome‐scale metabolic model by incorporating enzymatic constraints (2017) · cites this paper as Basan et al, 2015
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- Authors
- Basan, M., Hui, S., Okano, H., Zhang, Z., Shen, Y., Williamson, J. R., & Hwa, T.
- Affiliations
- ETH Zurich (CH)
- University of California San Diego (US)
- Scripps Research Institute (US)
- Venue
- Nature
- Published
- 2015-12
- Volume
- 528
- Issue
- 7580
- Pages
- 99-104
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4843128
- OpenAlex
- W2416065856
- Cited by
- 785
- References
- 60
- Citations by year
- 2026: 116 · 2025: 90 · 2024: 86 · 2023: 80 · 2022: 70 · 2021: 81 · 2020: 82 · 2019: 68 · 2018: 44 · 2017: 40 · 2016: 26 · 2015: 1
- FWCI
- 16.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM109069, R01GM095903)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- overflow metabolism, Warburg effect, Escherichia coli, fermentation, respiration, proteome allocation, protein abundance, biomass synthesis, metabolic modeling, bacterial growth, oxygen availability
- MeSH terms
- Energy Metabolism, Escherichia coli, Fermentation, Models, Biological, Neoplasms, Oxygen, Mass Spectrometry, Biomass, Cell Respiration, Acetic Acid, Proteome, Escherichia coli Proteins, Proteomics
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