Oxygen sensing

One of the more frequent changes all microorganisms face is a change in the external oxygen tension. Some organisms can adapt among oxygen concentrations equivalent to atmospheric levels and almost completely anoxic conditions. These facultative anaerobes such as E. coli, achieve this through changing the terminal electron acceptor used in oxidative phosphorylation. Under aerobic conditions they use water as a terminal electron acceptor and cytochrome aa3 oxidase. In the absence of oxygen and the presence of fumarate, cytochrome aa3 oxidase is switched off and the fumarate or nitrate system is switched on. The primary sensor for this oxygen-dependent switch is a regulatory protein called FNR (after fumarate and nitrate reduction). This is a global  regulator in that it alters the  transcriptional properties of hundreds of E. coli genes, acting as an inhibitor of some while elevating the transcription of others. The group of promoters and genes that are regulated by FNR are known collectively as the FNR regulon, and are all characterized by a distinct sequence in the relevant operator, an FNR binding site. Where FNR acts as an activator, the FNR binding site replaces the –35 sequence of the standard s70 promoter so that transcription cannot take place unless active FNR is present. The FNR binding site is found in a similar place to the LacI binding site when FNR is acting as a repressor.

The way in which FNR senses the presence of molecular oxygen is based more on chemistry than molecular biology.  In the  absence of oxygen,  a cluster of iron  and  sulfur  molecules forms at the  N-terminal end  of the  protein that allows  FNR to dimerize and interact with  DNA at  its specific binding sites.  When oxygen is present, the [2Fe-2S] ²⁺ cluster is destroyed and the protein can no longer function in DNA binding. This oxygen- sensing capability is carried out in concert with a number of other regulons such as the Arc cluster. CRP participates in another regulon as well and it is interesting to note that the binding sites for FNR and CRP differ through only one base pair, raising the possibility that a considerable amount of crosstalk occurs among regulatory systems, allowing the cell to simultaneously adapt too many conditions at once.