title: Production of 17-O-demethyl-geldanamycin, a cytotoxic ansamycin polyketide, by Streptomyces hygroscopicus DEM20745.
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.
authors.affiliation: a Faculty of Medical Sciences , Demuris Limited, Newcastle Biomedicine Bio-Incubators , Newcastle upon Tyne , UK.
authors.forename: Aron
authors.initials: A
authors.lastname: Baksh
authors.affiliation: a Faculty of Medical Sciences , Demuris Limited, Newcastle Biomedicine Bio-Incubators , Newcastle upon Tyne , UK.|b Industrial Doctorate Centre: Biopharmaceutical Process Development , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kepplinger
authors.affiliation: c School of Chemistry , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Hadiza A
authors.initials: HA
authors.lastname: Isah
authors.affiliation: c School of Chemistry , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Probert
authors.affiliation: c School of Chemistry , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: William
authors.initials: W
authors.lastname: Clegg
authors.affiliation: c School of Chemistry , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Wills
authors.affiliation: d School of Biology , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodfellow
authors.affiliation: e Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Jeff
authors.initials: J
authors.lastname: Errington
authors.affiliation: a Faculty of Medical Sciences , Demuris Limited, Newcastle Biomedicine Bio-Incubators , Newcastle upon Tyne , UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Allenby
authors.affiliation: c School of Chemistry , Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0001-6475-9161
authors.initials: MJ
authors.lastname: Hall
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism*; D005285:Fermentation; D007214:Indonesia; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D017828:Rifabutin / Q000378:metabolism; D012988:Soil Microbiology; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D017828:Rifabutin; C001277:geldanamycin
keywords: 17-O-demethyl-geldanamycin; actinomycete; ansamycin; cytotoxic; polyketide