Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 12477-12484 |
| Seitenumfang | 8 |
| Fachzeitschrift | Chemical science |
| Jahrgang | 11 |
| Ausgabenummer | 46 |
| Publikationsstatus | Veröffentlicht - 21 Okt. 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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- Allgemeine Chemie
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in: Chemical science, Jahrgang 11, Nr. 46, 21.10.2020, S. 12477-12484.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - The sporothriolides
T2 - A new biosynthetic family of fungal secondary metabolites
AU - Tian, Dong-Song
AU - Kuhnert, Eric
AU - Ouazzani, Jamal
AU - Wibberg, Daniel
AU - Kalinowski, Jörn
AU - Cox, Russell J.
N1 - Funding Information: This work was supported by the Chinese Scholarship Council [Dong-Song Tian (201706670001)] and the German Research Foundation (DFG INST 187/686-1 and CO 1328/4-1). This work benetted from the sharing of expertise within the DFG priority program “Taxon-Omics: New Approaches for Discovering and Naming Biodiversity” (SPP 1991). Prof. Marc Stadler (Helmholtz-Centre for Infection Research) and Dr Mark W Sumarah (London Research and Development Centre, Ottawa, Canada) are thanked for the gi of strains H. monticulosa MUCL 54604 and H. submonticulosa DAOMC 242471, respectively. Geraldine Le Goff is thanked for technical assistance. The bio-informatics support of the German Network for Bioinformatics Infrastructure (de.NBI) is gratefully acknowledged.
PY - 2020/10/21
Y1 - 2020/10/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097622358&partnerID=8YFLogxK
U2 - 10.1039/d0sc04886k
DO - 10.1039/d0sc04886k
M3 - Article
VL - 11
SP - 12477
EP - 12484
JO - Chemical science
JF - Chemical science
SN - 2041-6520
IS - 46
ER -