RT Journal Article SR Electronic T1 First-principles model of optimal translation factors stoichiometry JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.02.438287 DO 10.1101/2021.04.02.438287 A1 Jean-BenoƮt Lalanne A1 Gene-Wei Li YR 2021 UL http://biorxiv.org/content/early/2021/04/04/2021.04.02.438287.abstract AB Enzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that a parsimonious flux model constrained by proteome allocation is sufficient to predict the conserved ratios of translation factors through maximization of ribosome usage The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.Competing Interest StatementThe authors have declared no competing interest.