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

DOI: 10.1080/14786419.2016.1263854

Authors: Aron Baksh (Demurs Limited) , Bernhard Kepplinger (Newcastle University) , Hadiza A. Isah (Newcastle University) , Michael R. Probert (Newcastle University) , William Clegg (Newcastle University) , Corinne Wills (Newcastle University) , Michael Goodfellow (Newcastle University) , Jeff Errington (Newcastle University) , Nick Allenby (Demurs Limited) , Michael J. Hall (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Natural Product Research , VOL 31 , PAGES 1895-1900

State: Published (Approved)
Published: December 2016
Diamond Proposal Number(s): 6749

Abstract: 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.

Journal Keywords: 17-O-demethyl-geldanamycin, actinomycete, polyketide, ansamycin, cytotoxic

Subject Areas: Chemistry, Biology and Bio-materials, Medicine


Instruments: I19-Small Molecule Single Crystal Diffraction