## 2 Results
### Transcriptional Regulators and Sensory Histidine Kinases
#### 2.2.8. Cluster H: Regulatory Proteins More Abundant in Pi Limitation than in Pi  
Proficiency in _SL_ but Not in _SC_  
This cluster includes 11 regulatory proteins (Figure 9):  
* The response regulator MtrA/SCO3013 of the TCS SCO3013/SCO3012 (MtrB, HK) which, as PhoP, regulates both N and Pi metabolism. MtrA negatively auto-regulates its own expression and that of GlnR/SCO4159 [180; 181]. MtrA represses, in condition of N proficiency, the genes that are activated by GlnR/SCO4159 in condition of N limitation [181]. MtrA has a direct, but either positive or negative, impact on the expression of PhoRP and of other genes of Pi metabolism depending on the composition of the growth medium [182]. MtrA also binds to sites located in the promoter regions of genes encoding pathway specific activators Actll-Orf-1, Actll-Orf4, and RedZ and has a negative impact on their expression and thus on ACT and RED biosynthesis [183]. It also represses the expression of _blindD_ (sub-cluster D3) that plays a positive role in the regulation of antibiotic biosynthesis [125]. In contrast, MtrA activates the expression of genes involved in formation of aerial mycelium, including _clp_, _rdl_, and _ram_ and regulatory genes of the Bld and Whi families [184]. MtrA thus positively controls morphological differentiation and negatively antibiotic production.  
Figure 8: Cluster G, heatmap representation of transcriptional regulators and sensory histidine kinases more abundant in Pi proficiency than in Pi limitation in _SL_ but not in _SC_.  
The regulator AbsC/SCO5405 plays a role in Zinc (Zn) homeostasis since it negatively controls, together with Zur (cluster F), the expression of the cluster directing the biosynthesis of the zincophore, coelibactin, and of another NRPS cluster with predicted siderophore-like activity [185]. The deletion of AbsC results in elevated expression of these clusters and thus higher Zn availability. Since Zn was shown to have a negative impact on antibiotic biosynthesis [145], the negative impact that AbsC exerts on antibiotic production is thought to be due to enhanced Zn availability [185]. Furthermore, numerous enzymes belonging to carbon and nitrogen metabolism were more abundant in an AbsC mutant suggesting that AbsC negatively regulates their expression [186]. Consistently, most of the enzymes of central carbon and nitrogen metabolism listed in [186] and thought to be under the negative control of AbsC were indeed more abundant in Pi proficiency, when the expression of AbsC is low [9], than in Pi limitation. The cause of the low abundance of AbsC in _SC_ is unknown but is likely to have important consequences on the cellular metabolism of this strain. The gene encoding the sensory HK SCO5829 of the TCS SCO5829/SC5828 (RR) is located downstream of a gene encoding sucrose/ferredoxin-like protein SCO5830 and SCO5831 a citrate synthase-like protein. SCO5831 was clearly more abundant in Pi proficiency than in Pi limitation in _SL_ (Figure 4 of [9]) suggesting that this TCS might repress SCO5831 expression in Pi limitation in _SL_. Finally, the three cold shock proteins (Csps) SCO0527/ScoF, SCO3731/ScoF1, and SCO4325/CspB were also highly expressed in _SL_ in Pi limitation. Originally, Csps were viewed as nucleic acid chaperons preventing the formation of secondary structures in mRNA at low temperature and thus facilitating the initiation of translation but since the expression of some Csps was shown to be non-cold inducible, they are now viewed as involved in the adaptation to various stresses [187].