Fig. 8

Graphic abstract of the regulation of subtilin biosynthesis in B. subtilis W168. Structural gene spaS encodes subtilin pre-peptide, which is subjected to post-translational modification by SpaBC and export by SpaT. On the trans side of the cell membrane the leader peptide of subtilin precursor is cleaved off by unspecific proteases, resulting in bioactive subtilin molecule. Subtilin is constitutively expressed at low level, and strongly repressed by transition state regulator AbrB in a SigH-independent manner (except for spaBTC). During growth, the cell density is increasing and accompanied by an increased subtilin concentration, which results from the loss of the repression of spa genes by AbrB which is repressed by Spo0A as the cell enters transition phase. When a threshold concentration is reached, subtilin acting as a peptide pheromone activates the TCS SpaRK, which in turn induces subtilin gene expression for both subtilin biosynthesis (spaS and spaBTC) and self-immunity (spaIFEG), fulfilling the autoregulatory circuit of subtilin biosynthesis