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The sporothriolides. A new biosynthetic family of fungal secondary metabolites.


ABSTRACT: The biosynthetic gene cluster of the antifungal metabolite sporothriolide 1 was identified from three producing ascomycetes: Hypomontagnella monticulosa MUCL 54604, 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.

SUBMITTER: Tian DS 

PROVIDER: S-EPMC8162735 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The sporothriolides. A new biosynthetic family of fungal secondary metabolites.

Tian Dong-Song DS   Kuhnert Eric E   Ouazzani Jamal J   Wibberg Daniel D   Kalinowski Jörn J   Cox Russell J RJ  

Chemical science 20201021 46


The biosynthetic gene cluster of the antifungal metabolite sporothriolide <b>1</b> was identified from three producing ascomycetes: <i>Hypomontagnella monticulosa</i> MUCL 54604, <i>H. spongiphila</i> CLL 205 and <i>H. submonticulosa</i> 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. <i>In vitro</i> reactions showed th  ...[more]

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