The proteome is a terminal electron acceptor
Abstract
Microbial metabolism is impressively flexible, enabling growth even when available nutrients differ greatly from biomass in redox state. E. coli, for example, rearranges its physiology to grow on reduced and oxidized carbon sources through several forms of fermentation and respiration. To understand the limits on and evolutionary consequences of metabolic flexibility, we developed a mathematical model coupling redox chemistry with principles of cellular resource allocation. Our integrated model clarifies key phenomena, including demonstrating that autotrophs grow slower than heterotrophs because of constraints imposed by intracellular production of reduced carbon. Our model further indicates that growth is improved by adapting the redox state of biomass to nutrients, revealing an unexpected mode of evolution where proteins accumulate mutations benefiting organismal redox balance.
Copyright and License
Data Availability
Code Availability
All code and data are available either as supplementary tables or at https://github.com/flamholz/redox-proteome.
Acknowledgement
We are grateful to E. Afik, L. Aristilde, J. Ciemniecki, A. Duarte, J. Goldford, S. Hirokawa, R. Murali, T. Roeschinger, and G. Salmon for useful discussions and to Y.M. Bar-On, G. Chure, D. LaRowe, and R. Milo for detailed comments on the manuscript.
Funding
NSF PHY-1748958 to the Kavli Institute for Theoretical Physics (AIF, AG)
Jane Coffin Childs Memorial Fund postdoctoral fellowship 61-1772 (AIF).
Gordon and Betty Moore Foundation grant GBMF4513 (AG)
Govt of India’s Ramalingaswami Fellowship (AG).
Caltech Center for Evolutionary Sciences (WWF)
National Institutes of Health grant 1R01AI127850-01A1 (DKN)
The Rosen Center at Caltech (RP)
National Institutes of Health MIRA grant 1R35 GM118043 (RP)
Contributions
Conceptualization: AIF
Methodology: AIF, AG
Investigation: AIF, AG, WWF, DKN, RP
Visualization: AIF, AG
Funding acquisition: AIF, AG, WWF, DKN, RP
Supervision: WWF, DKN, RP
Writing – original draft: AIF
Writing – review & editing: AIF, AG, WWF, DKN, RP
Conflict of Interest
The authors declare no competing interests.
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Additional details
- PMCID
- PMC10862836
- National Science Foundation
- PHY-1748958
- Jane Coffin Childs Memorial Fund for Medical Research
- 61-1772
- Gordon and Betty Moore Foundation
- GBMF4513
- Government of India
- Ramalingaswami Fellowship
- California Institute of Technology
- Caltech Center for Evolutionary Science
- National Institutes of Health
- 1R01AI127850-01A1
- California Institute of Technology
- Donna and Benjamin M. Rosen Bioengineering Center
- National Institutes of Health
- 1R35 GM118043
- Caltech groups
- Division of Biology and Biological Engineering, Division of Geological and Planetary Sciences, Caltech Center for Evolutionary Science, Rosen Bioengineering Center