Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum

Publication: Research - peer-reviewJournal article – Annual report year: 2012

  • Author: Sørensen, Jens Laurids

    Aarhus University, Denmark

  • Author: Hansen, Frederik Teilfeldt

    Aarhus University, Denmark

  • Author: Sondergaard, Teis Esben

    Aarhus University, Denmark

  • Author: Staerk, Dan

    University of Copenhagen, Denmark

  • Author: Lee, T. Verne

    University of Auckland, New Zealand

  • Author: Wimmer, Reinhard

    Aalborg University, Denmark

  • Author: Klitgaard, Louise Graabæk

    Aarhus University, Denmark

  • Author: Purup, Stig

    Aarhus University, Denmark

  • Author: Giese, Henriette

    Aarhus University, Denmark

  • Author: Frandsen, Rasmus John Normand

    Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark

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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.
Original languageEnglish
JournalEnvironmental Microbiology
Issue number5
Pages (from-to)1159-1170
StatePublished - 2012
CitationsWeb of Science® Times Cited: 40
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ID: 9657766