Abstract
Summary The advent of environmental O 2 about 2.5 billion years ago forced microbes to metabolically adapt and to develop mechanisms for O 2 sensing. Sensing of O 2 by [4Fe–4S] 2+ to [2Fe–2S] 2+ cluster conversion represents an ancient mechanism that is used by FNR Ec ( Escherichia coli ), FNR Bs ( Bacillus subtilis ), NreB Sa ( Staphylococcus aureus ) and WhiB3 Mt ( Mycobacterium tuberculosis ). The phylogenetic relationship of these sensors was investigated. FNR Ec homologues are restricted to the proteobacteria and a few representatives from other phyla. Homologues of FNR Bs and NreB Sa are located within the bacilli, of WhiB3 within the actinobacteria. Archaea contain no homologues. The data reveal no similarity between the FNR Ec , FNR Bs , NreB Sa and WhiB3 sensor families on the sequence and structural levels. These O 2 sensor families arose independently in phyla that were already present at the time O 2 appeared, their members were subsequently distributed by lateral gene transfer. The chemistry of [4Fe–4S] and [2Fe–2S] cluster formation and interconversion appears to be shared by the sensor protein families. The type of signal output is, however, family specific. The homologues of FNR Ec and NreB Sa vary with regard to the number of Cys residues that coordinate the cluster. It is suggested that the variants derive from lateral gene transfer and gained other functions.