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

Lookup NU author(s): Dr Bernhard Kepplinger, Hadiza Isah, Dr Mike Probert, Emeritus Professor Bill Clegg, Dr Corinne Wills, Emeritus Professor Michael Goodfellow, Professor Jeff Errington, Dr Nicholas Allenby, Dr Michael Hall

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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 significant potential for direct use in anticancer therapy and is a key starting material for the semi-synthesis of GDM analogues. This preferential biosynthesis of 17-O-DMG facilitates easy access to this important molecule and provides further insight the biosynthesis of the geldanamycins.


Publication metadata

Author(s): Baksh A, Kepplinger B, Isah H, Probert MR, Clegg W, Wills C, Goodfellow M, Errington J, Allenby N, Hall MJ

Publication type: Article

Journal: Natural Product Research

Year: 2017

Volume: 31

Issue: 16

Pages: 1895-1900

Online publication date: 14/12/2016

Acceptance date: 05/11/2016

ISSN (print): 1478-6419

ISSN (electronic): 1478-6427

Publisher: Taylor & Francis

URL: http://dx.doi.org/10.1080/14786419.2016.1263854

DOI: 10.1080/14786419.2016.1263854


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