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Production of 17-O-demethyl-geldanamycin, a cytotoxic ansamycin polyketide, by Streptomyces hygroscopicus DEM20745

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journal contribution
posted on 14.12.2016 by Aron Baksh, Bernhard Kepplinger, Hadiza A. Isah, Michael R. Probert, William Clegg, Corinne Wills, Michael Goodfellow, Jeff Errington, Nick Allenby, Michael J. Hall

The actinomycete DEM20745, collected from non-rhizosphere soil adjacent to Paraserianthes falactaria trees (Cangkringan, Indonesia), is an efficient producer of the anticancer ansamycin polyketide 17-O-demethyl-geldanamycin (17-O-DMG), a biosynthetic precursor of the Hsp90 inhibitor geldanamycin (GDM). In DEM20745, 17-O-DMG is the major ansamycin product observed reaching a maximum titre of 17 mg/L in the fermentation broth. 17-O-DMG has the potential to be a key starting material for the semi-synthesis of GDM analogues for use in anticancer therapy. Thus, this preferential biosynthesis of 17-O-DMG facilitates easy access to this important molecule and provides further insight in the biosynthesis of the geldanamycins.