title: Breaking the silence: protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans.
abstract: The genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs.
authors.affiliation: Abteilung für Molekulare Mikrobiologie & Genetik, Institut für Mikrobiologie & Genetik, Georg August Universität, Göttingen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gerke
authors.forename: Ozgür
authors.initials: O
authors.lastname: Bayram
authors.forename: Kirstin
authors.initials: K
authors.lastname: Feussner
authors.forename: Manuel
authors.initials: M
authors.lastname: Landesfeind
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shelest
authors.forename: Ivo
authors.initials: I
authors.lastname: Feussner
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism; D001688:Biological Products / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D008666:Metalloendopeptidases