(239b) Metabolic Tradeoffs in Resource Investment and Function: A Switch or a Dial?

An economics-based analysis of stoichiometric metabolic models quantified a continuum of molecular-level, resource allocation tradeoff strategies that permit competitive cellular functioning under continuous gradients of nutrient scarcities. The theoretical biochemical pathway resource requirements differ between distinct nutrient limitations as well as across the severity of the considered stress.  The approach provides attractive ecological explanations for a variety of well-known physiological responses to specific culturing conditions, as well as the ability to extract a relatively small number of biologically important flux distributions from a stoichiometric model’s enormous steady-state solution set.  The reduced solution space provides biological insights on better fits  of a variety of quantitative flux measurements than are possible using other published cellular objective functions, but published data for further testing the graduated nature of these predictions is surprisingly lacking. The presented work fills some of that gap, generating and examining the experimental proteomic and physiological responses of Escherichia coli to four levels of iron, nitrogen, and carbon restriction.  The results provide a theoretical basis for the relative strength of evolutionary selection for optimality as well as metabolic simplicity, and additionally suggest alternative approaches to the redirection of metabolism for industrial applications.