Krastel P~Hoepfner D, 2015

Pubmed ID 26179970
Title Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties.
Authors Philipp Krastel, Silvio Roggo, Markus Schirle, Nathan T Ross, Francesca Perruccio, Peter Aspesi, Thomas Aust, Kathrin Buntin, David Estoppey, Brigitta Liechty, Felipa Mapa, Klaus Memmert, Howard Miller, Xuewen Pan, Ralph Riedl, Christian Thibaut, Jason Thomas, Trixie Wagner, Eric Weber, Xiaobing Xie, Esther K Schmitt, Dominic Hoepfner
Abstract Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF-1α) as the primary target for this compound class. Nannocystin A (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti-cancer compound didemnin B on EF-1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.
Citation Angew. Chem. Int. Ed. Engl. 2015; 54:10149-54


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Papers Phenotype Conditions Collection Tested mutants Data Details
Krastel P~Hoepfner D, 2015 growth (relative abundance in pooled culture) nannocystin [75 uM] hom 4,509 Quantitative
Krastel P~Hoepfner D, 2015 growth (relative abundance in pooled culture) nannocystin [75 uM] het 5,748 Quantitative

Curation history

May 25, 2017 Tested strains to load.
May 25, 2017 Data to load.
May 31, 2017 Tested strains loaded.
May 31, 2017 Data loaded.