Is Transcriptional Regulation of Metabolic Pathways an Optimal Strategy for Fitness?

BACKGROUND: Transcriptional regulation of the genes in metabolic pathways is a highly successful strategy, which is virtually universal in microorganisms. The lac operon of E. coli is but one example of how enzyme and transporter production can be made conditional on the presence of a nutrient to catabolize. METHODOLOGY: With a minimalist model of metabolism, cell growth and transcriptional regulation in a microorganism, we explore how the interaction between environmental conditions and gene regulation set the growth rate of cells in the phase of exponential growth. This in silico model, which is based on biochemical rate equations, does not describe a specific organism, but the magnitudes of its parameters are chosen to match realistic values. Optimizing the parameters of the regulatory system allows us to quantify the fitness benefit of regulation. When a second nutrient and its metabolic pathway are introduced, the system must further decide whether and how to activate both pathways. CONCLUSIONS: Even the crudest transcriptional network is shown to substantially increase the fitness of the organism, and this effect persists even when the range of nutrient levels is kept very narrow. We show that maximal growth is achieved when pathway activation is a more or less steeply graded function of the nutrient concentration. Furthermore, we predict that bistability of the system is a rare phenomenon in this context, but outline a situation where it may be selected for.