title: A transposon-based strategy to identify the regulatory gene network responsible for landomycin E biosynthesis.
abstract: We report here a transposon-based strategy to generate Streptomyces globisporus 1912 mutants with improved landomycin E production. The modified minitransposon with strong, outward-oriented promoters for the overexpression of downstream-situated genes has been applied for mutant library generation. Approximately 2500 mutants of S. globisporus 1912 were analyzed for landomycin E production, leading to the identification of several overproducers. Subcloning and sequencing of the sites of integration showed that some of the inactivated genes encode proteins with a similarity to known bacterial regulators such as TetR and LuxR families. One of the regulators (GntR type) has shown the strongest influence on the landomycin E production. Its ortholog (encoded by sco3269) in Streptomyces coelicolor was characterized in greater detail and showed similar effects on actinorhodin production and morphological differentiation.
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Saarbrücken 66123, Germany.
authors.forename: Lilya
authors.initials: L
authors.lastname: Horbal
authors.forename: Viktor
authors.initials: V
authors.lastname: Fedorenko
authors.forename: Andreas
authors.initials: A
authors.lastname: Bechthold
authors.forename: Andriy
authors.initials: A
authors.lastname: Luzhetskyy
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D053898:Biosynthetic Pathways / Q000235:genetics*; D004251:DNA Transposable Elements; D005798:Genes, Bacterial; D005809:Genes, Regulator; D060847:Metabolic Engineering / Q000379:methods; D016254:Mutagenesis, Insertional / Q000379:methods*; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D004251:DNA Transposable Elements; C113593:landomycin E