The sporothriolides: A new biosynthetic family of fungal secondary metabolites

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Dong-Song Tian
  • Eric Kuhnert
  • Jamal Ouazzani
  • Daniel Wibberg
  • Jörn Kalinowski
  • Russell J. Cox

External Research Organisations

  • ICSN Institut de Chimie des Substances Naturelles
  • Bielefeld University
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Details

Original languageEnglish
Pages (from-to)12477-12484
Number of pages8
JournalChemical science
Volume11
Issue number46
Publication statusPublished - 21 Oct 2020

Abstract

The biosynthetic gene cluster of the antifungal metabolite sporothriolide 1 was identified from three producing ascomycetes: Hypomontagnella monticulosa MUCL 546, H. spongiphila CLL 205 and H. submonticulosa DAOMC 242471. A transformation protocol was established, and genes encoding a fatty acid synthase subunit and a citrate synthase were simultaneously knocked out which led to loss of sporothriolide and sporochartine production. In vitro reactions showed that the sporochartines are derived from non-enzymatic Diels-Alder cycloaddition of 1 and trienylfuranol A 7 during the fermentation and extraction process. Heterologous expression of the spo genes in Aspergillus oryzae then led to the production of intermediates and shunts and delineation of a new fungal biosynthetic pathway originating in fatty acid biosynthesis. Finally, a hydrolase was revealed by in vitro studies likely contributing towards self-resistance of the producer organism.

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Cite this

The sporothriolides: A new biosynthetic family of fungal secondary metabolites. / Tian, Dong-Song; Kuhnert, Eric; Ouazzani, Jamal et al.
In: Chemical science, Vol. 11, No. 46, 21.10.2020, p. 12477-12484.

Research output: Contribution to journalArticleResearchpeer review

Tian, D-S, Kuhnert, E, Ouazzani, J, Wibberg, D, Kalinowski, J & Cox, RJ 2020, 'The sporothriolides: A new biosynthetic family of fungal secondary metabolites', Chemical science, vol. 11, no. 46, pp. 12477-12484. https://doi.org/10.1039/d0sc04886k
Tian, D.-S., Kuhnert, E., Ouazzani, J., Wibberg, D., Kalinowski, J., & Cox, R. J. (2020). The sporothriolides: A new biosynthetic family of fungal secondary metabolites. Chemical science, 11(46), 12477-12484. https://doi.org/10.1039/d0sc04886k
Tian DS, Kuhnert E, Ouazzani J, Wibberg D, Kalinowski J, Cox RJ. The sporothriolides: A new biosynthetic family of fungal secondary metabolites. Chemical science. 2020 Oct 21;11(46):12477-12484. doi: 10.1039/d0sc04886k
Tian, Dong-Song ; Kuhnert, Eric ; Ouazzani, Jamal et al. / The sporothriolides : A new biosynthetic family of fungal secondary metabolites. In: Chemical science. 2020 ; Vol. 11, No. 46. pp. 12477-12484.
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abstract = "The biosynthetic gene cluster of the antifungal metabolite sporothriolide 1 was identified from three producing ascomycetes: Hypomontagnella monticulosa MUCL 546, H. spongiphila CLL 205 and H. submonticulosa DAOMC 242471. A transformation protocol was established, and genes encoding a fatty acid synthase subunit and a citrate synthase were simultaneously knocked out which led to loss of sporothriolide and sporochartine production. In vitro reactions showed that the sporochartines are derived from non-enzymatic Diels-Alder cycloaddition of 1 and trienylfuranol A 7 during the fermentation and extraction process. Heterologous expression of the spo genes in Aspergillus oryzae then led to the production of intermediates and shunts and delineation of a new fungal biosynthetic pathway originating in fatty acid biosynthesis. Finally, a hydrolase was revealed by in vitro studies likely contributing towards self-resistance of the producer organism.",
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