The proteome acts as a terminal electron acceptor

Microbial metabolism contributes to growth in two key, interrelated ways. Bioenergetic processes like respiration exploit favorable redox transformations (e- transfers) to extract energy from the environment, generating ATP to power homeostasis and biosynthesis. At the same time, metabolic transformations convert nutrients – e.g. ammonia, phosphate, and sugars – into the macromolecules that build cells, e.g. proteins, nucleic acids, and lipids. I will describe a simple mathematical model of resource allocation during microbial growth that explicitly accounts for these dual roles by tracking the nominal oxidation state of carbon (NOSC) in nutrients (e.g. glucose), intermediates (amino acids), products (CO₂), and biomass (proteins). Tracking NOSC permits the model to enforce redox homeostasis (balancing of e- flows) and to distinguish between respirations, which require an external terminal e- acceptor like O₂, and fermentations, which do not. Incorporating the ATP yields of bioenergetic pathways and ATP costs of biosynthesis into the model predicts that a relatively reduced proteome, carrying more e-/carbon, would be advantageous during fast growth, as it promotes redox homeostasis without occupying ribosomes to produce specific enzymes. I will show how recent proteomic surveys support this prediction in heterotrophs (E. coli) and photoautotrophs (Synechocystis), indicating that the chemical and resource-economic views of microbial physiology should be integrated more fully.