## 2 Results
### Transcriptional Regulators and Sensory Histidine Kinases
Sub-cluster B2 includes:
* Three proteins involved in the regulation of phosphate metabolism: the TCS PhoR/PhoP as well as the regulatory protein PhoU/SCO4228. In condition of Pi limitation, PhoR/PhoP positively controls the expression of genes of the Pho regulon involved in Pi scavenging and up-take [80] and negatively those involved in nitrogen assimilation [81]. This TCS also plays a negative role in the control of morphological differentiation and antibiotic production [82; 83]. PhoU, through its interaction with PstB, the ATP-binding cassette of the high affinity ABC Pi transporter PstSCAB, was proposed to sense environmental Pi and to transmit this signal to the SHK PhoR, promoting or inhibiting its auto-phosphorylation in Pi limitation or proficiency, respectively [84; 85]. The difference in the abundance of proteins involved in Pi scavenging and up-take, in conditions of in Pi limitation or proficiency, was much greater in _SL_ than in _SC_ (Figure 6 of [9]). * The adenyltransferase GlnE/SCO2234 that modulates the activity of the glutamine synthase GSI through adenylylation, in response to N availability [86] and is thus involved in the regulation of nitrogen metabolism. * The LacI regulator SCO4158 [87] whose encoding gene is located downstream of _glnR/sco4159_ encoding a major regulator of N metabolism (cluster G). SCO4158 was abundant in both strains in Pi limitation whereas GlnR was far more abundant in Pi proficiency than in Pi limitation in _SL_ but poorly abundant in _SC_ in both Pi conditions. Considering the proximity of _sco4158_ and _glnR_ and their opposite regulatory features, SCO4158 might regulate _glnR_ expression. Proteins involved in N assimilation were clearly more abundant, but only slightly more abundant, in Pi proficiency than in Pi limitation, in _SL_ and _SC_, respectively (Figures 6 and 7 of [9]). This suggested that, besides the relieve of repression of the expression of these genes by PhoP in condition of Pi proficiency, an activator of the expression of these genes might be either missing or non-functional in _SC_ (see Discussion). The pleiotropic regulator Crp/SCO3571 [88, 89] and the regulator AtrA/SCO4118 [90] both have a positive impact on ACT biosynthesis via their direct interaction with the promoter region of _actII-ORF4_. The gene encoding the GntR regulator SCO1728 is located in divergence of a gene encoding a putative mycothi synthase that might play a role in the resistance to OxS. In the condition of over-expression, SCO1728 was shown to have a negative impact on antibiotic production [91], which might be linked to its role in the resistance to OxS that was proposed to be an important trigger of ACT biosynthesis [8, 12]. The MarR regulator SCO0487/Cchl, whose encoding gene is present in the biosynthetic pathway of the peptide siderophore, coelichelin (_sc00499/cchA--sc00489/cchK_) [92]. The \(11\) proteins of the coelichelin cluster detected (Figure S12B of [9]) were, as SCO0487, all more abundant in Pi limitation than in Pi proficiency in _SL_, suggesting that SCO0487 positively regulates their expression in Pi limitation. Five of these proteins (SCO0493 to SCO0497) were also more abundant in Pi limitation than in Pi proficiency in _SC_ whereas, unexpectedly, four others (SCO0492, SCO0498 to SCO0490) were more  
Figure 3: Cluster B, heatmap representation of transcriptional regulators and sensory histidine kinases more abundant in Pi limitation than in Pi proficiency in both strains. Cluster B that can be divided into 3 sub-clusters B1, B2 and B3. Sub-cluster B1 includes 6 proteins more abundant in _SC_ than in _SL_ in both Pi conditions but also abundant in _SL_ in Pi limitation at 48h. Sub-cluster B2 includes 22 proteins more abundant in Pi limitation than in Pi proficiency in both strains. Sub-cluster B3 includes 7 regulators more abundant in Pi limitation than in Pi proficiency at 48 h and 60 h in _SL_ and _SC_, respectively, and more abundant in _SL_ than in _SC_ in Pi proficiency.