title: Flavoproteins are potential targets for the antibiotic roseoflavin in Escherichia coli.
abstract: The riboflavin analog roseoflavin is an antibiotic produced by Streptomyces davawensis. Riboflavin transporters are responsible for roseoflavin uptake by target cells. Roseoflavin is converted to the flavin mononucleotide (FMN) analog roseoflavin mononucleotide (RoFMN) by flavokinase and to the flavin adenine dinucleotide (FAD) analog roseoflavin adenine dinucleotide (RoFAD) by FAD synthetase. In order to study the effect of RoFMN and RoFAD in the cytoplasm of target cells, Escherichia coli was used as a model. E. coli is predicted to contain 38 different FMN- or FAD-dependent proteins (flavoproteins). These proteins were overproduced in recombinant E. coli strains grown in the presence of sublethal amounts of roseoflavin. The flavoproteins were purified and analyzed with regard to their cofactor contents. It was found that 37 out of 38 flavoproteins contained either RoFMN or RoFAD. These cofactors have different physicochemical properties than FMN and FAD and were reported to reduce or completely abolish flavoprotein function.
authors.affiliation: Department of Biotechnology, Institute for Technical Microbiology, Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Langer
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Birgit
authors.initials: B
authors.lastname: Hobl
authors.forename: Tilo
authors.initials: T
authors.lastname: Mathes
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000032:analysis / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012256:Riboflavin / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005420:Flavoproteins; D011994:Recombinant Proteins; C576819:roseoflavin mononucleotide; D005182:Flavin-Adenine Dinucleotide; C009191:roseoflavin; D017853:Phosphotransferases (Alcohol Group Acceptor); C022532:riboflavin kinase; D009713:Nucleotidyltransferases; C020143:FMN adenylyltransferase; D012256:Riboflavin