Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties†
2015
Cultivation of
myxobacteriaof the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of
elongation factor 1.
Whole genome sequenceanalysis 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 factor1α (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 Bon EF-1α. This myxobacterial
chemotypethus offers an interesting starting point for further investigations of the potential of therapeutics targeting
elongation factor 1.
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