Global Regulatory Systems Operating in Bacilysin Biosynthesis in Bacillus subtilis

Abstract

In <i>Bacillus subtilis</i>, bacilysin is a nonribosomally synthesized dipeptide antibiotic composed of <i>L</i>-alanine and <i>L</i>-anticapsin. The biosynthesis of bacilysin depends on the <i>bacABCDEywfG </i>operon (<i>bac</i> operon)and the adjacent <i>ywfH</i> gene. To elucidate the effects of global regulatory genes on the expression of <i>bac</i> operon, we used the combination of <i>lacZ </i>fusion analysis and the gel mobility shift assays. The cell density-dependent transition state induction of the <i>bac</i> operon was clearly shown. The basal expression level of the <i>bac </i>operon as well as transition state induction of <i>bac</i> is directly ComA dependent. Three Phr peptides, PhrC, PhrF and PhrK, are required for full-level expression of ComA-dependent <i>bac</i> operon expression, but the most important role seemed to be played by PhrC in stimulating <i>bac</i> expression through a RapC-independent manner. Spo0A is another positive regulator which participates in the transition state induction of <i>bac</i> both directly by interacting with the <i>bac</i> promoter and indirectly by repressing <i>abrB </i>expression. AbrB and CodY proteins do not only directly repress the <i>bac</i> promoter, but they also mutually stimulate the transition state induction of <i>bac </i>indirectly<i>, </i>most likely by antagonizing their repressive effects without preventing each other’s binding since both proteins can bind to the <i>bac</i> promoter simultaneously.