Phenotypic repertoire of the FNR regulatory network in Escherichia coli

The FNR protein in Escherichia coli is an O₂ sensor that modifies global gene expression to adapt the cell to anaerobic growth. Regulation of FNR involves continuous cycling of the protein between its active and inactive states under aerobic conditions without apparent function. This raises the question of what benefit to the overall life cycle might compensate for the cost of cycling and reveals that the role of this process is poorly understood. To address this problem, we introduce the concept of a 'system design space', which provides a rigorous definition of phenotype at the molecular level and a means of visualizing the phenotypic repertoire of the system. Our analysis reveals undesirable and desirable phenotypes with an optimal constellation of parameter values for the system. To facilitate a more concrete understanding of what the design space represents, we analyse mutations that alter the apparent dimerization rate constant of FNR. We show that our estimated wild-type value of this rate constant, which is difficult to measure in situ, is located within this constellation and that the behaviour of the system is compromised in mutants if the value of the apparent dimerization rate constant lies beyond the bounds of this optimal constellation.