PT  - JOURNAL ARTICLE
AU  - Matteo Mori
AU  - Enzo Marinari
AU  - Andrea De Martino
TI  - A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth
AID  - 10.1101/113183
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 113183
4099  - http://biorxiv.org/content/early/2017/03/02/113183.short
4100  - http://biorxiv.org/content/early/2017/03/02/113183.full
AB  - 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.