Title: 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.