Identification of the non-ribosomal peptide synthetase responsible for biosynthesis of the potential anti-cancer drug sansalvamide in Fusarium solani

Patricia Romans-Fuertes, Teis Esben Sondergaard, Manuela Ilse Helga Sandmann, Rasmus Dam Wollenberg, Kristian Fog Nielsen, Frederik T. Hansen, Henriette Giese, Ditlev Egeskov Brodersen, Jens Laurids Sørensen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Sansalvamide is a cyclic pentadepsipeptide produced by Fusarium solani and has shown promising results as potential anti-cancer drug. The biosynthetic pathway has until now remained unidentified, but here we used an Agrobacterium tumefaciens-mediated transformation (ATMT) approach to generate knockout mutants of two candidate non-ribosomal peptide synthetases (NRPS29 and NRPS30). Comparative studies of secondary metabolites in the two deletion mutants and wild type confirmed the absence of sansalvamide in the NRPS30 deletion mutant, implicating this synthetase in the biosynthetic pathway for sansalvamide. Sansalvamide is structurally related to the cyclic hexadepsipeptide destruxin, which both contain an α-hydroxyisocaproic acid (HICA) unit. A gene cluster responsible for destruxin production has previously been identified in Metarhizium robertsii together with a hypothetical biosynthetic pathway. Using comparative bioinformatic analyses of the catalytic domains in the destruxin and sansalvamide NRPSs, we were able to propose a model for sansalvamide biosynthesis. Orthologues of the gene clusters were also identified in species from several other genera including Acremonium chrysogenum and Trichoderma virens, which suggests that the ability to produce compounds related to destruxin and sansalvamide is widespread.
    Original languageEnglish
    JournalCurrent Genetics
    Volume62
    Issue number4
    Pages (from-to)799-807
    Number of pages9
    ISSN0172-8083
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Agrobacterium tumefaciens-mediated transformation
    • Destruxin
    • Metarhizium robertsii
    • Nectria haematococca
    • NRPS
    • Secondary metabolites

    Fingerprint

    Dive into the research topics of 'Identification of the non-ribosomal peptide synthetase responsible for biosynthesis of the potential anti-cancer drug sansalvamide in <i>Fusarium solani</i>'. Together they form a unique fingerprint.

    Cite this