title: Waking up Streptomyces secondary metabolism by constitutive expression of activators or genetic disruption of repressors.
abstract: Streptomycete bacteria are renowned as a prolific source of natural products with diverse biological activities. Production of these metabolites is often subject to transcriptional regulation: the biosynthetic genes remain silent until the required environmental and/or physiological signals occur. Consequently, in the laboratory environment, many gene clusters that direct the biosynthesis of natural products with clinical potential are not expressed or at very low level preventing the production/detection of the associated metabolite. Genetic engineering of streptomycetes can unleash the production of many new natural products. This chapter describes the overexpression of pathway-specific activators, the genetic disruption of pathway-specific repressors, and the main strategy used to identify and characterize new natural products from these engineered Streptomyces strains.
authors.affiliation: Génétique et Microbiologie, UMR UL-INRA 1128, IFR110 EFABA, Université de Lorraine, Vandœuvre-lès-Nancy, France. bertrand.aigle@univ-lorraine.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Aigle
authors.forename: Christophe
authors.initials: C
authors.lastname: Corre
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D005818:Genetic Engineering / Q000379:methods*; D018942:Macrolides / Q000378:metabolism; D055442:Metabolome; D005810:Multigene Family; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001688:Biological Products; D018942:Macrolides; D010455:Peptides; D012097:Repressor Proteins; D014157:Transcription Factors; C558882:stambomycin B; C014097:methylenomycin A