## 3 Gene Regulation in _Bacillus_  
Gene regulation of LPBSs produced by _Bacillus_ spp. has been most intensively investigated within the surfactin biosynthesis system (Figure 3). Expression of the gene _srfA_ is controlled by several peptide pheromones including ComX and Phr [106]. _B. subtilis_ encodes eight Phr peptides (PhrA, PhrC [CSF], PhrE, PhrF, PhrG, PhrH, PhrI, and PhrK) and 11 aspartyl-phosphate phosphatase proteins (RapA to RapK). Each Phr peptide inhibits the activity of cotranscribed Rap protein. RapC, RapF, and RapK act as negative regulators of _srfA_[107]. ComX interacts with the membrane-bound histidine kinase ComP, which autophosphorylates upon stimulation and then transfers its phosphate to a serine residue in the response regulator ComA. The phosphorylated ComA binds to ComA boxes (T/GCGG-N4-CCGCA) upstream of the _srfA_ promoter as a tetramer and initiates transcription of _srfA_[108, 109]. Recently, it was found that ComA binds to a degenerate tripartite sequence consisting of three recognition elements (RE). RE1 and RE2 contain the inverted repeats previously characterized as part of the ComA-boxes. Meanwhile, RE3 is located downstream of RE1 and RE2 with a consensus sequence identical to that of RE1 [110]. In addition, mutation at three non-aspartate amino acids in the _N_-terminal portion of ComA decreases surfactin production [111]. These three amino acids may be involved in the phosphorylation mechanism. It was previously reported that glucose can stimulate the transcription of _comA_ and consequently increases the expression of _srfA_[112, 113]. Induction of _srfA_ requires the oligopeptide permease Spo0K, which is involved in PhrC import [114]. On the other hand, expression of _srfA_ is downregulated upon treatment with H\({}_{2}\)O\({}_{2}\); this evidence led to identification of the H\({}_{2}\)O\({}_{2}\) stress responsive regulator PerR. PerR positively regulates _srfA_ expression by binding to PerR boxes located in the upstream region of ComA boxes in which H\({}_{2}\)O\({}_{2}\) inhibits the DNA-binding activity of PerR [115]. Furthermore, the chaperon subunit ClpX and protease ClpP are required for the transcription of _srfA_ at a step that follows ComP-dependent activation of ComA [116]. An additional transcription factor DegU also functions as a positive regulator for _srfA_ transcription [117]. Overexpression of RapD, RapG, and RapH inhibits _srfA_ transcription, and production of these Rap proteins is suppressed by RghR [118, 119]. Mutation in _sodA_, which encodes superoxide dismutase, inhibits transcription of the comQXP quorum-sensing locus, thereby preventing _srfA_ expression [120]. At high concentrations of amino acids such as Ile, Leu, and Val, CodY represses transcription of _srfA_ by interacting specifically with the _srfA_ promoter [121]. Like CodY, AbrB also negatively regulates _srfA_ transcription. Expression of _srfA_ is also repressed by the RNA polymerase-binding protein Spx [122]. On the other hand, the Spx-RNA polymerase interaction is required for positive transcriptional control of genes in response to thiol-oxidative stress [123]. Furthermore, 4'-phosphopantetheinyl transferase (Sfp/PPTase) is required for the activation of SrfA enzymes by converting the inactive _apo_-forms of the T-domains to the active _holo_-forms [124]. An acyltransferase SrfA-Te is also required in the initial step of transferring a hydroxyl fatty acid to the first amino acid in the peptide. The surfactin self-resistance protein, YerP, is required for surfactin exportation [125]. Regulation of the fengycin/plipastatin genes is positively controlled by DegQ, an enhancer of extracellular protease production [126]. _degQ_ is a pleiotropic regulatory gene that controls the production of several hydrolytic enzymes [127]. Production of plipastatin is severely reduced in the _degQ_ mutant, but no significant change is observed in surfactin production. A Sfp-like protein, Lpa-8, is also required for plipastatin production in _B. subtilis_ YB8 [128]. Overexpression of _degQ_ in _B.