(601e) Physiological, Proteomic, and in Silico Cost-Benefit Analysis of Resource-Limited Growth

Evolutionary selection has produced fit microbes capable of adapting their metabolic functioning to cope with competitive environments while utilizing limited resource pools. Physiological and proteomic characteristics of Escherichia coli cultures grown in either nitrogen- or iron-limited chemostat conditions were predicted and interpreted using an in silico cost-benefit analysis. The in silico analysis used ecological theory that examines resource allocation strategies that maximize fitness. All potential strategies for investing nitrogen and iron into the metabolic machinery of E. coli were enumerated by decomposing the metabolic network into a complete listing of non-divisible, mathematically-defined biochemical pathways. The enzymatic resource investment requirements for each distinct pathway were examined in concert with the pathway's efficiency at converting substrate into biomass. Allocating limiting resources to perform one function well typically comes at the cost of performing other metabolic functions well. The analysis identified competitive molecular-level tradeoffs between pathway resource requirements and metabolic efficiency that are likely important to ecological versatility. Experimental chemostat data illustrated that under nitrogen- and iron-limited conditions E. coli regulates its metabolism to invest the limiting resource competitively at the cost of optimal biomass yields on electron donor. The study highlights fundamental design considerations for effective control and engineering of microbes for bioprocess and biomedical applications.