title: Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression.
abstract: Riboswitches in messenger RNAs carry receptor domains called aptamers that can bind to metabolites and control expression of associated genes. The Gram-positive bacterium Bacillus subtilis has two representatives of a class of riboswitches that bind flavin mononucleotide (FMN). These riboswitches control genes responsible for the biosynthesis and transport of riboflavin, a precursor of FMN. We found that roseoflavin, a chemical analog of FMN and riboflavin that has antimicrobial activity, can directly bind to FMN riboswitch aptamers and downregulate the expression of an FMN riboswitch-lacZ reporter gene in B. subtilis. A role for the riboswitch in the antimicrobial mechanism of roseoflavin is supported by our observation that some previously identified roseoflavin-resistant bacteria have mutations within an FMN aptamer. Riboswitch mutations in these resistant bacteria disrupt ligand binding and derepress reporter gene expression in the presence of either riboflavin or roseoflavin. If FMN riboswitches are a major target for roseoflavin antimicrobial action, then future efforts to develop compounds that trigger FMN riboswitch function could lead to the identification of new antimicrobial drugs.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Lee
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Blount
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D001483:Base Sequence; D005486:Flavin Mononucleotide / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D012256:Riboflavin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; C009191:roseoflavin; D005486:Flavin Mononucleotide; D012256:Riboflavin