Identification of StiR, the first regulator of secondary metabolite formation in the myxobacterium Cystobacter fuscus Cb f17.1.

Myxobacteria are well established as proficient producers of natural products with numerous biological activities. Although some knowledge has been gained regarding the biosynthesis of secondary metabolites in this class of bacteria, almost nothing is known about the underlying regulatory mechanisms. In order to identify regulatory elements, we submitted the argyrin and stigmatellin producer Cystobacter fuscus to a random transposon mutagenesis strategy and screened 1,000 mutants for the occurrence of strains showing remarkably increased or decreased production of these compounds. In addition to the identification of the stigmatellin biosynthetic gene cluster, a novel positive regulator (stiR) of stigmatellin production was identified after transposon recovery. In order to exclude secondary mutagenesis effects, a double cross-over mutagenesis strategy was applied to the strain resulting in the repeated generation of the transposon genotype. This strain was shown to be equally effected in natural product biosynthesis.