Experimental and in Silico Analysis of Competitive Metabolic Network Structure-Function Relationships

Experimental and theoretical analyses of Escherichia coli cultured under nutrient limiting conditions were used to evaluate ecologically competitive metabolic network structure-function relationships relevant to designing bioprocesses or controlling problematic pathogens. An in silico analysis of central metabolism was used to identify resource allocation strategies that maximize fitness through molecular-level tradeoffs in pathway resource requirements and metabolic efficiency. The in silico predictions were tested using physiological and proteomic data collected from E. coli cultures grown using 12 distinct nutrient-limited chemostat conditions. Consistent with theory, experimental data demonstrated that under iron-, nitrogen-, or carbon-limited growth conditions E. coli regulates its metabolism to invest the limiting resource competitively at the cost of other resources like for instance electron donor. The economics-based analysis quantified a continuum of resource allocation strategies that permit competitive cellular functioning under gradients of nutrient scarcities. The results provide a theoretical basis for adaptive optimality as well as metabolic simplicity, and additionally suggest engineering blueprints to redirect metabolism for industrial applications.