title: Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum.
abstract: Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F. graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.
authors.affiliation: Department of Animal Science, Faculty of Science and Technology, Aarhus University, Blichers Allé 20, Tjele, Denmark. jls@bio.aau.dk
authors.forename: Jens Laurids
authors.initials: JL
authors.lastname: Sørensen
authors.forename: Frederik Teilfeldt
authors.initials: FT
authors.lastname: Hansen
authors.forename: Teis Esben
authors.initials: TE
authors.lastname: Sondergaard
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
authors.forename: T Verne
authors.initials: TV
authors.lastname: Lee
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wimmer
authors.forename: Louise Graabaek
authors.initials: LG
authors.lastname: Klitgaard
authors.forename: Stig
authors.initials: S
authors.lastname: Purup
authors.forename: Henriette
authors.initials: H
authors.lastname: Giese
authors.forename: Rasmus John Normand
authors.initials: RJ
authors.lastname: Frandsen
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000633:toxicity; D005670:Fusarium / Q000201:enzymology* / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D009154:Mutation; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D048630:Polyketide Synthases