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Sagar Gore

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About Sagar Gore:

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SEEK ID: https://data.chembiosys.de/people/82

Location: Germany

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Joined: 13th Oct 2016

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Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute

Country: Germany

City: Jena

Web page: http://www.leibniz-hki.de

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Melleolides impact fungal translation via elongation factor 2.

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Sagar Gore

Oliver Werz

Christian Hertweck

Dirk Hoffmeister

Abstract (Expand)

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 Delta2,4-double bond present in dihydroarmillylorsellinate (DAO) or arnamial, for example. Yet, the mode of action of Delta2,4-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.

Authors: M. Dorfer, D. Heine, S. Konig, S. Gore, O. Werz, C. Hertweck, M. Gressler, D. Hoffmeister

Date Published: 15th May 2019

Publication Type: Journal

PubMed ID: 31042251

Citation: Org Biomol Chem. 2019 May 15;17(19):4906-4916. doi: 10.1039/c9ob00562e.

Created: 10th May 2021 at 13:49

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