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

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  • Patricia Romans-Fuertes, Department of Chemistry and Bioscience, Aalborg Universitet
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  • Teis Esben Sondergaard, Aalborg Universitet
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  • Manuela Ilse Helga Sandmann, Aalborg Universitet
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  • Rasmus Dam Wollenberg, Aalborg Universitet
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  • Kristian Fog Nielsen, Danmarks Tekniske Universitet
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  • Frederik T. Hansen
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  • Henriette Giese, Department of Chemistry and Bioscience, Aalborg Universitet
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  • Ditlev Egeskov Brodersen
  • Jens Laurids Sørensen, Department of Chemistry and Bioscience, Aalborg Universitet

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
Issue4
Pages (from-to)799-807
Number of pages9
ISSN0172-8083
DOIs
Publication statusPublished - 1 Nov 2016

    Research areas

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

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