Evolutionary success requires strategic allocation of scarce resources. Under conditions of nutrient sufficiency, metabolic networks are well known to be regulated for thermodynamic efficiency however; efficient biochemical pathways are anabolically expensive to construct. A cost-benefit analysis of an in silico Escherichia coli network revealed the relationship between pathway proteome synthesis requirements, thermodynamic efficiency, substrate affinity, and DNA coding sequence length. Pathway proteome synthesis requirements appear to have shaped metabolic network structure and regulation. Under conditions of nutrient scarcity and other general stresses, E. coli expresses pathways with relatively inexpensive proteome synthesis requirements instead of more efficient but also anabolically more expensive pathways. This evolutionary strategy provides a cellular function-based explanation for common network motifs like isozymes and parallel pathways and possibly explains ‘overflow' metabolisms observed during nutrient scarcity. The study provides fundamental clues into evolutionary pressures and competitive metabolic designs.

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