## 2 Results
### Transcriptional Regulators and Sensory Histidine Kinases
#### 2.2.3 Cluster C: Regulators More Abundant in _SC_ than in _SL_ in Both Pi Conditions
Glucosamine-6-phosphate (GlcN-6P) and N-acetylglucosamine-6-phosphate (GlcNAc-6P) act as allosteric effectors of DasR impairing binding to operator sites and thus allowing the expression of the DasR-target genes. Since several enzymes involved in cell wall degradation were far more abundant in \(SC\) than in \(SL\) (Figure S10, cluster C of [9]), GlcN-6P as GlcNAc-6P are likely to result from the autolytic degradation of peptidoglycan that obviously takes place in \(SC\) but not in \(SL\). * The RR MacR/SCO2120 of the TCS MarS/MarR positively controls the expression of several membrane proteins involved in maintenance of cell wall integrity of some proteins involved in primary carbon metabolism and of proteins of the Zur regulon which plays a role in zinc homeostasis [110; 111]. Furthermore, MacR was shown to directly interact with the _actII-orf4_ promotor region and to have a positive impact on ACT, as well as CDA and RED biosynthesis [111]. * The RR RapA1/SCO5403 of the TCS RapA2/RapA1, which has a positive impact on CPK and ACT biosynthesis [112]. * BldC/SCO4091, which has a positive impact on antibiotic production and morphological differentiation [113; 114]. * The ScbR-like regulator SlbR/SCO608 which, in interaction with \(\gamma\)-butyrolactone SCB1, binds to the promoter regions of _scbR/A_ and _adpA_[115] and inhibits the transcription of these genes that positively control morphological development and antibiotic production [116]. SlbR thus has an indirect negative impact on antibiotic production and morphological differentiation [117]. The 18 regulators of sub-cluster D2 were more abundant in Pi proficiency than in Pi limitation at both time points in \(SC\) but some of them were also abundant in Pi limitation at 60 h in \(SL\). This sub-cluster includes:  
* The RR OrrA/SCO3008 of the TCS OhkA(SCO1596, cluster C)/OrrA involved in osmoadaptation that has a negative impact on RED and ACT biosynthesis [99; 100]. * The starvation sensing protein SpaA/SCO7629, an orthologique of the _E. coli_ protein RpsA involved in an homoserine lactone signaling pathway [118] that has a positive impact on antibiotic biosynthesis [119]. * The gene encoding the regulator SCO2152 is located in divergence of the _qcrCAB_ operon (_sco2148-sco2151_), which plays an important role in growth and development of \(SC\) in conditions of oxygen limitation [120; 121]. SCO2152 was rather more abundant in \(SC\) than in \(SL\) in both Pi conditions, whereas QcrA/SCO2149 showed an opposite trend (Figure 5 of [9] and Figure S1) suggesting that SCO2152 might negatively regulate the expression of the _qcrCAB_ operon. The 10 regulators of sub-cluster D3 were also more abundant in Pi proficiency than in Pi limitation at both time points in _SC_ but some of them were also abundant in Pi limitation at 60 h in _SL_. This cluster includes the phosphohistidine phosphatase SixA/SC01809 whose function is unknown in Streptomyces and the pleiotropic regulator BldD/SCO1489, whose DNA binding activity is modulated by the signaling molecule c-di-GMP [122; 123]. BldD has a positive impact on antibiotic production and morphological differentiation [124]. The  
Figure 5: Cluster D, heatmap representation of transcriptional regulators and sensory histidine kinases more abundant in Pi proficiency than in Pi limitation in SC. Cluster D that can be divided into 3 sub-clusters D1, D2 and D3. The 18 regulators of sub-cluster D1 were more abundant in Pi proficiency than in Pi limitation at both time points in _SC_ but some of them were also abundant in Pi limitation at 48 h in SC. The 18 regulators of sub-cluster D2 were more abundant in Pi proficiency than in Pi limitation at both time points in _SC_ but some of them were also abundant in Pi limitation at 60 h in _SL_. The 10 regulators of sub-cluster D3 were more abundant in Pi proficiency than at both time points in _SC_ but some of them were also abundant in Pi limitation at 60 h in _SL_.