title: Discovery of microbial natural products by activation of silent biosynthetic gene clusters.
abstract: Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities and a wide variety of applications in medicine and agriculture, such as the treatment of infectious diseases and cancer, and the prevention of crop damage. Genomics has revealed that many microorganisms have far greater potential to produce specialized metabolites than was thought from classic bioactivity screens; however, realizing this potential has been hampered by the fact that many specialized metabolite biosynthetic gene clusters (BGCs) are not expressed in laboratory cultures. In this Review, we discuss the strategies that have been developed in bacteria and fungi to identify and induce the expression of such silent BGCs, and we briefly summarize methods for the isolation and structural characterization of their metabolic products.
authors.affiliation: School of Chemistry, The University of Sydney, New South Wales 2006, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rutledge
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Challis
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D005810:Multigene Family; D037941:Silencer Elements, Transcriptional / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products