The protein translation machinery is expressed for maximal efficiency in Escherichia coli

Protein synthesis is the most expensive process in fast-growing bacteria. The economic aspects of protein synthesis at the cellular level have been investigated by estimating ribosome activity and the expression of ribosomes, tRNA, mRNA, and elongation factors. The observed growth-rate dependencies form the basis of powerful phenomenological bacterial growth laws; however, a quantitative theory allowing us to understand these phenomena on the basis of fundamental biophysical and biochemical principles is currently lacking. Here, we show that the observed growth-rate dependence of the concentrations of ribosomes, tRNAs, mRNA, and elongation factors in Escherichia coli can be predicted accurately by minimizing cellular costs in a detailed mathematical model of protein translation; the mechanistic model is only constrained by the physicochemical properties of the molecules and requires no parameter fitting. We approximate the costs of molecule species through their masses, justified by the observation that cellular dry mass per volume is roughly constant across growth rates and hence represents a limited resource. Our results also account quantitatively for observed RNA/protein ratios and ribosome activities in E. coli across diverse growth conditions, including antibiotic stresses. Our prediction of active and free ribosome abundance facilitates an estimate of the deactivated ribosome reserve, which reaches almost 50% at the lowest growth rates. We conclude that the growth rate dependent composition of E coli9s protein synthesis machinery is a consequence of natural selection for minimal total cost under physicochemical constraints, a paradigm that might generally be applied to the analysis of resource allocation in complex biological systems.