FIG. 4.

Model for the regulation of heme homeostasis by the two-component system HrrSA in C. glutamicum. Under conditions of sufficient iron supply, the global iron regulator DtxR represses expression of the response regulator hrrA, heme uptake systems (htaA and hmuTUV), and heme oxygenase (hmuO), an enzyme involved in the release of heme iron. Under iron limitation, expression of hrrA increases. In this study, we could show that the two-component system HrrSA of C. glutamicum is involved in the heme-dependent activation of hmuO and genes encoding heme-containing protein complexes of the respiratory chain. Furthermore, HrrA directly represses transcription of genes coding for heme biosynthesis enzymes (for operon prediction, see http://coryneregnet.cebitec.uni-bielefeld.de). The signal sensed by the sensor kinase HrrS is not yet known, but heme itself or a heme-related metabolite is likely. Not included in this model is the postulated repression of the CgtSR8 two-component system by HrrSA, which is currently under investigation and might disclose a further level of complexity in this regulatory network.