The proteome is a terminal electron acceptor (A. Flamholz). Today, two distinct frameworks are used to understand microbial growth. One approach treats microbes as coupling redox reactions to conserve energy in order to form biomass from available nutrients. Another describes the allocation of cells’ finite biosynthetic capacity to different catalytic roles --- e.g., transport, catabolism, protein synthesis --- to achieve particular metabolic rates. These frameworks have distinct strengths: redox naturally describes a diversity of metabolic chemistries, while resource allocation explains the existence of intrinsic maximum growth rates, for example. I will introduce a unified redox-based resource allocation model framework that links microbial physiology to environmental chemistry. Assembling integrated models of respiration, fermentation, and photosynthesis clarified key microbiological phenomena, including i) explaining why autotrophs grow more slowly than heterotrophs, and ii) outlining key constraints on fermentative growth. Our model further predicted that heterotrophic growth is improved by matching the C redox state of biomass to the local environment. Through analysis of 60,000 genomes and diverse proteomic datasets, I found evidence that proteins indeed accumulate amino acid substitutions promoting redox matching. I therefore propose an unexpected mode of genome evolution where substitutions neutral or even deleterious to proteins’ individual biochemical or structural functions of proteins can nonetheless be selected due to a redox-chemical benefit to the organism — a “function-independent” mode of protein evolution.

Paper DOI: https://doi.org/10.1073/pnas.2404048121

See for more information on Avi Flamholz, Frank Bruggeman, Maaike Remeijer, and Martina dal Bello.

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