## 4 Gene Regulation in _Pseudomonas_  
Similar to ComP/ComA in _Bacillus_, a two-component system has been identified as the master transcriptional regulation system in _Pseudomonads_ (Figure 4). Typically, this system consists of a sensor kinase GacS and response regulator GacA. GacS was first described in _P. syringae_ pv. _syringae_ B728a as an essential factor for lesion manifestation. Meanwhile, GacA was first identified as a global activator of antibiotic and cyanide production in _P. fluorescens_ CHA0 [133]. It is proposed that upon interaction with the signal(s), GacS is activated by autophosphorylation and then GacA acts as a phosphoryl acceptor. After trans-phosphorylation, GacA activates transcription of the regulatory gene, which in turn controls the expression of target genes [133]. Based on bacterial two-hybrid analysis, the entire GacA molecule is necessary for GacA interaction with itself or GacS [134]. The GacS/GacA system positively controls the expression of genes required for the synthesis of lipopolysaccharide (syringomycin, amphiisin, putisolvin, and entolysin) because mutation in either gene impairs lipoprotein production [65, 135, 136, 137, 138]. A quorum-sensing system that triggers GacA/GacS phosphorylation during high cell density is essential for biosynthesis of the lipoprotein putisolvin [139]. In Gram-negative bacteria, the quorum-sensing system largely relies on the interaction of signaling molecule _N_-acyl homoserine lactones (AHLs) that are synthesized via LuxI protein with the transcriptional regulator LuxR. The quorum-sensing system in _P. putida_ PCL1445 is composed of LuxI-homologous PpuI, LuxR-homologous PpuR, and RasL. Expression of the genes _ppuI_ and _ppuR_ are required for the biosynthesis of AHLs, and mutation of these genes reduces putisolvin production. Meanwhile, overproduction of AHLs and putisolvin is observed in the _rsaL_ mutant. This observation suggests that RasL acts as a repressor of PpuI and PpuR. In contrast, biosynthesis of the lipopeptides mastestolide, amphiisin, and syringomycin is not regulated by AHL-based quorum sensing [48]. Downstream of the Gac system, the cognate transcriptional regulator LuxR regulates the production of several lipopeptides that bind to the operator of the NRPS genes. LuxR protein contains a DNA-binding helix-turn-helix motif in its _C_-terminal region. In _Pseudomonas_ sp. MIS38, the LuxR-type transcription factor, ArfF, positively controls transcription of the gene _arf_[140]. LuxR-type protein is also implicated in the biosynthesis of entolysin, putisolvin, and syringafactin, and mutation of this gene results in the loss of lipopeptide production [65, 68, 105, 141]. Two types of LuxR-type proteins are involved in biosynthesis of syringomycin, syringopeptin, and viscosoin. SalA and SyrF are the LuxR-type proteins responsible for the production of two lipopeptides, syringomycin and syringopeptin, in _P. syringae_ pv. _syringae_ B301D. SalA is suggested to control transcription of SyrF, an apparent homolog of ArfF, and SyrF binds and trans-activates the target NRPS promoter [142]. Mutation of two LuxR-type proteins in _P. fluorescens_ SBW25, ViscAR and ViscBCR, results in the reduction of NRPS gene transcription and loss of viscosoin production [143]. Recently, heat shock proteins were shown to regulate biosynthesis of putisolvin and arthrofactin [140, 141]. Mutation in the gene encoding DnaK, a HSP70 class heat shock protein, impairs putisolvin production in _P. putida_ PCL1445. Together with DnaJ, DnaK regulates putisolvin synthesis at low temperature. Elimination of arthrofactin synthesis was identified following mutation of the gene encoding HtpG, a HSP90 class heat shock protein. However, normal expression of the arthrofactin synthetase genes is retained in the HtpG mutant. Thus, HtpG appears to be involved in the proper folding of positive transcription factors or in the assembly of the NRPS complex. The serine protease ClpP regulates massetolide biosynthesis in _P.