The RFN riboswitch of Bacillus subtilis is a target for the antibiotic roseoflavin produced by Streptomyces davawensis

The riboflavin (vitamin B-2) biosynthetic genes in Bacillus subtilis are transcribed simultaneously from the riboflavin promoter (P-rib. The 5'-end of the nascent rib-mRNA carries a flavin mononucleotide (FMN) binding riboswitch, which regulates gene expression. The antibiotic roseoflavin from Streptomyces davawensis is a naturally occurring riboflavin analog, its mechanism of action is largely unknown. A recombinant B. subtilis strain carrying a copy of P-rib-RFN fused to a promoterless lacZ reporter gene in the chromosomal amyE locus was grown in a minimal medium. Upon addition of roseoflavin to the growth medium the apparent LacZ activity in this strain was not significantly reduced. Similar experiments carried out on recombinant R subtilis strains oversynthesizing the flavin transporters RibU (B. subtilis) or RIM (S. davawensis) produced still other results. In these strains, roseoflavin (as well as riboflavin) repressed LacZ synthesis indicating that the RFN riboswitch is a target for roseoflavin (or roseoflavin mononucleotide), which may at least in part explain its antibiotic activity.