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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