A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

Abstract

Many microbial systems are known to actively reshape their proteomes in response to changes in growth conditions induced e.g. by nutritional stress or antibiotics. Part of the re-allocation accounts for the fact that, as the growth rate is limited by targeting specific metabolic activities, cells simply respond by fine-tuning their proteome to invest more resources into the limiting activity (i.e. by synthesizing more proteins devoted to it). However, this is often accompanied by an overall re-organization of metabolism, aimed at improving the growth yield under limitation by re-wiring resource through different pathways. While both effects impact proteome composition, the latter underlies a more complex systemic response to stress. By focusing on E. coli's acetate switch, we use mathematical modeling and a re-analysis of empirical data to show that the transition from a predominantly fermentative to a predominantly respirative metabolism in carbon-limited growth results from the trade-off between maximizing the growth yield and minimizing its costs in terms of required the proteome share. In particular, E. coli's metabolic phenotypes appear to be Pareto-optimal for these objective functions over a broad range of dilutions.