The sporothriolides. A new biosynthetic family of fungal secondary metabolites

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 s...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2020-12, Vol.11 (46), p.12477-12484
Main Authors: Tian, Dong-Song, Kuhnert, Eric, Ouazzani, Jamal, Wibberg, Daniel, Kalinowski, Jörn, Cox, Russell J
Format: Article
Language:English
Subjects:
Analytical chemistry
Biosynthesis
Chemical Sciences
Chemistry
Cycloaddition
Fatty acids
Fermentation
Fungi
Fungicides
Gene expression
Genes
Metabolites
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Summary: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. A new family of fungal biosynthetic pathways is elucidated based on the use of fatty acid and citrate-like intermediates.
ISSN:2041-6520
2041-6539
DOI:10.1039/d0sc04886k