Identification of the non-ribosomal peptide synthetase responsible for biosynthesis of the potential anti-cancer drug sansalvamide in Fusarium solani
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- 作者：Patricia Romans-Fuertes ; Teis Esben Sondergaard…
- 关键词：Nectria haematococca ; NRPS ; Secondary metabolites ; Agrobacterium tumefaciens ; mediated transformation ; Metarhizium robertsii ; Destruxin
- 刊名：Current Genetics
- 出版年：2016
- 出版时间：November 2016
- 年：2016
- 卷：62
- 期：4
- 页码：799-807
- 全文大小：655 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Microbial Genetics and Genomics
Microbiology
Biochemistry
Cell Biology
Plant Sciences
Proteomics - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0983
- 卷排序：62
文摘
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.