title: Riboflavin analogs as antiinfectives: occurrence, mode of action, metabolism and resistance.
abstract: Antimetabolites are molecules, which are structurally similar to molecules needed to carry out primary metabolic reactions.The inhibitory activity of an antimetabolite depends on its successful competition with the natural substrate, ligand, modulator or cofactor of a given biomolecule. Antimetabolites are indispensable as molecular tools in order to understand biological processes. Beyond that,antimetabolites have a large variety of applications in the pharmaceutical and food industries. The identification of the structural riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates that anti-vitamins/cofactor analogs may serve as lead structures for the development of novel antibiotics. The latter is supported by the recent finding that roseoflavin had a profound inhibiting effect on the growth and infectivity of the human bacterial pathogen Listeria monocytogenes at very low concentrations. Roseoflavin is studied in our laboratory as a model compound. We investigate the biosynthesis, the possible large-scale production, the metabolization,the mechanism of action and the resistance mechanism of the producer organism in order to pave the way for the structured analysis of other vitamin analogs yet to be discovered. These compounds hopefully will help to replenish the arsenal of antimicrobials urgently needed to fight multiresistant bacterial pathogens.
authors.affiliation: Institute for Technical Microbiology, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
authors.forename: Danielle Biscaro
authors.initials: DB
authors.lastname: Pedrolli
authors.forename: Frank
authors.initials: F
authors.lastname: Jankowitsch
authors.forename: Julia
authors.initials: J
authors.lastname: Schwarz
authors.forename: Simone
authors.initials: S
authors.lastname: Langer
authors.forename: Shinobu
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Eva
authors.initials: E
authors.lastname: Frei
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial; D006801:Humans; D015394:Molecular Structure; D012256:Riboflavin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D012256:Riboflavin