ArticleProceedings of the National Academy of Sciences of the United States of America2025
Global constraint principle for microbial growth laws.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Cell geometry and membrane protein crowding constrain Escherichia coli growth rate, overflow metabolism, respiration, and maintenance energy.FEBS letters · 2026Article
- Weakest link epistasis and the geometry of genetic load.bioRxiv : the preprint server for biology · 2026Article
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Abstract
Understanding complex living systems requires identifying universal phenomenological laws that are independent of species and molecular-biological details. The Monod equation is a cornerstone of phenomenological microbial growth laws, depicting the growth rate as a saturating function of a single substrate. Because of its similarity in functional form to the Michaelis-Menten equation, cellular growth is often thought to be limited by a single reaction. However, cellular growth generically results from the coordination of thousands of metabolic reactions and diverse intracellular limited resources. Consequently, the mechanistic origins of the Monod equation remain controversial, and its extension has encountered limitations. Here, we propose the global constraint principle for cellular growth: As one nutrient becomes more available, other intracellular resources become limiting, driving transitions to distinct modes of resource allocation. Based on a general framework of constraint-based modeling and its dual formulations, we mathematically prove that, in general, microbial growth kinetics curves are monotonically increasing and concave with respect to nutrient availability. Numerical simulations using genome-scale
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