Activation of dormant secondary metabolism neotrehalosadiamine synthesis by an RNA polymerase mutation in Bacillus subtilis

Abstract

Microorganisms possess the ability to produce a variety of commercially important secondary metabolites such as antibiotics. Although it becomes harder and harder to discover useful new compounds, microorganisms still have the potential to produce unknown compounds. One of the reasons for the difficulty in finding new compounds is that the expression level of many secondary metabolite genes is insufficient in wildtype strains. Therefore, a new method of activating gene expression might be a powerful tool for the screening of novel compounds and for strain improvement to overproduce useful compounds. We found that the rifampicin-resistant RNA polymerase mutations stimulate the expression of antibiotic synthetic gene clusters in several microorganisms. In the case of the Grampositive model organism Bacillus subtilis, one of the rifampicin-resistance mutations resulted in the activation of a dormant secondary metabolism, neotrehalosadiamine synthesis. To clarify this activation mechanism, we first identified the neotrehalosadiamine biosynthetic operon and investigated its transcriptional regulation. Here we summarize our findings on the transcriptional regulation of the neotrehalosadiamine biosynthetic operon and discuss a crucial effect of the rifampicinresistance mutation on the expression of dormant genes.