Paper
Melleolides impact fungal translation via elongation factor 2.
Published May 15, 2019 · DOI · Maximilian Dörfer, D. Heine, Stefanie König
Organic & biomolecular chemistry
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Abstract
Melleolides from the honey mushroom Armillaria mellea represent a structurally diverse group of polyketide-sesquiterpene hybrids. Among various bioactivites, melleolides show antifungal effects against Aspergillus and other fungi. This bioactivity depends on a Δ2,4-double bond present in dihydroarmillylorsellinate (DAO) or arnamial, for example. Yet, the mode of action of Δ2,4-unsaturated, antifungal melleolides has been unknown. Here, we report on the molecular target of DAO in the fungus Aspergillus nidulans. Using a combination of synthetic chemistry to create a DAO-labelled probe, protein pulldown assays, MALDI-TOF-based peptide analysis and western blotting, we identify the eukaryotic translation elongation factor 2 (eEF2) as a binding partner of DAO. We confirm the inhibition of protein biosynthesis in vivo with an engineered A. nidulans strain producing the red fluorescent protein mCherry. Our work suggests a binding site dissimilar from that of the protein biosynthesis inhibitor sordarin, and highlights translational elongation as a valid antifungal drug target.
Melleolides from Armillaria mellea inhibit Aspergillus nidulans protein biosynthesis by binding to eEF2, highlighting translational elongation as a valid antifungal drug target.
- PopulationOlder adults (50-71 years)
- Sample size24
- MethodsObservational
- OutcomesBody Mass Index projections
- ResultsSocial networks mitigate obesity in older groups.
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