Figure 3.

Regulatory scheme and dynamic response of the C. glutamicum heme detoxification module. A. Scheme of the regulatory interactions considered in the mathematical model for the heme detoxification module. Uptake of external heme molecules via HmuTUV and subsequent consumption/incorporation via diverse enzymes is crucial for bacterial growth under iron starvation. The fine‐tuned response to heme in order to avoid intoxication is mainly based on the two TCSs ChrSA and HrrSA. The two kinases ChrS and HrrS are autophosphorylated in response to external hemin. After activation, they (cross‐)phosphorylate the response regulator ChrA. In addition, the non‐phosphorylated form of ChrS functions as a phosphatase on the phosphorylated response regulator ChrA. The phosphorylated response regulator activates expression of its target genes hrtBA and chrSA. The gene product of hrtBA is a heme exporter that transports internal heme to the extracellular space. B. Dynamical response of our computational model for the detoxification module (Supplementary Text; Model equations M1) toward different external heme levels, as given by the simulation of specific fluorescence of a P_hrtBA‐eyfp reporter, normalized to the maximal specific fluorescence at 4 μM heme. C. Experimental dynamical response of a P_hrtBA‐eyfp reporter in wild‐type C. glutamicum cells toward different heme concentrations supplied in the medium at t = 0 h. [Colour figure can be viewed at wileyonlinelibrary.com]