RT Journal Article SR Electronic T1 Proteome efficiency of metabolic pathways in Escherichia coli increases along the nutrient flow JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.13.516329 DO 10.1101/2022.11.13.516329 A1 Xiao-Pan Hu A1 Stefan Schroeder A1 Martin J. Lercher YR 2022 UL http://biorxiv.org/content/early/2022/11/15/2022.11.13.516329.abstract AB Understanding the allocation of the cellular proteome to different cellular processes is central to unraveling the organizing principles of bacterial physiology. Proteome allocation to protein translation itself is maximally efficient, i.e., it represents the minimal allocation of dry mass able to sustain the observed protein production rate. In contrast, recent studies on bacteria have demonstrated that the concentrations of many proteins exceed the minimal level required to support the observed growth rate, indicating some heterogeneity across pathways in their proteome efficiency. Here, we systematically analyze the proteome efficiency of metabolic pathways, which together account for more than half of the E. coli proteome during exponential growth. Comparing the predicted minimal and the observed proteome allocation to different metabolic pathways across growth conditions, we find that the most costly biosynthesis pathways – those for amino acid biosynthesis and cofactor biosynthesis – are expressed for near optimal efficiency. Overall, proteome efficiency increases along the carbon flow through the metabolic network: proteins involved in pathways of nutrient uptake and central metabolism tend to be highly over-abundant, while proteins involved in anabolic pathways and in protein translation are much closer to the expected minimal abundance across conditions. Our work thus provides a bird’s-eye view of metabolic pathway efficiency, demonstrating systematic deviations from optimal cellular efficiency at the network level.Importance Protein translation is the most expensive cellular process in fast-growing bacteria, and efficient proteome usage should thus be under strong natural selection. However, recent studies show that a considerable part of the proteome is unneeded for instantaneous cell growth in E. coli. We still lack a systematic understanding of how this excess proteome is distributed across different pathways as a function of the growth conditions. We estimated the minimal required proteome across growth conditions in E. coli and compared the predictions with experimental data. We found that the proteome allocated to the most expensive internal pathways, including translation and the synthesis of amino acids and cofactors, are near the minimally required levels. In contrast, transporters and central carbon metabolism show much higher proteome levels than the predicted minimal abundance. Our analyses show that the proteome fraction unneeded for instantaneous cell growth decreases along the nutrient flow in E. coli.Competing Interest StatementThe authors have declared no competing interest.