A delayed mass-action model for the transcriptional control of Hmp, an NO detoxifying enzyme, by the iron-sulfur protein FNR

Permission to archive accepted author manuscript. Embargo in effect until 2021In Escherichia coli, an enzyme called Hmp is a key contributor to the detoxification of nitric oxide (NO). In the absence of NO, the transcription of the hmp gene is repressed by an iron-sulfur protein called FNR. NO damages the iron-sulfur cluster of FNR, weakening the repression of hmp and allowing expression of Hmp to high levels. A delayed mass-action model for the Hmp-FNR network has been developed. This model has 33 parameters, all but three of which were estimated. One of the unknown parameters, the rate of NO inflow into the cell’s cytoplasm, was used as a control parameter in a study of the steady-state structure of this model. This study revealed bistability across a wide range of inflow rates, oxygen concentrations, and values of the unknown parameters. The bistability is caused by substrate inhibition of Hmp by NO, which allows for a high-NO steady state, which would likely be lethal, to coexist with a biologically desirable low-NO steady state