title: Activation and products of the cryptic secondary metabolite biosynthetic gene clusters by rifampin resistance (rpoB) mutations in actinomycetes.
abstract: A subset of rifampin resistance (rpoB) mutations result in the overproduction of antibiotics in various actinomycetes, including Streptomyces, Saccharopolyspora, and Amycolatopsis, with H437Y and H437R rpoB mutations effective most frequently. Moreover, the rpoB mutations markedly activate (up to 70-fold at the transcriptional level) the cryptic/silent secondary metabolite biosynthetic gene clusters of these actinomycetes, which are not activated under general stressful conditions, with the exception of treatment with rare earth elements. Analysis of the metabolite profile demonstrated that the rpoB mutants produced many metabolites, which were not detected in the wild-type strains. This approach utilizing rifampin resistance mutations is characterized by its feasibility and potential scalability to high-throughput studies and would be useful to activate and to enhance the yields of metabolites for discovery and biochemical characterization.
authors.affiliation: Hiroshima Institute of Technology, Department of Life Science, Saeki-ku, Hiroshima, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Kasahara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirose
authors.forename: Kiriko
authors.initials: K
authors.lastname: Murakami
authors.forename: Rie
authors.initials: R
authors.lastname: Kugimiya
authors.forename: Kozo
authors.initials: K
authors.lastname: Ochi
mesh_terms: D039903:Actinobacteria / Q000187:drug effects* / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D012293:Rifampin