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

Nat Prod Res. 2017 Aug;31(16):1895-1900. doi: 10.1080/14786419.2016.1263854. Epub 2016 Dec 14.

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.

Keywords: 17-O-demethyl-geldanamycin; actinomycete; ansamycin; cytotoxic; polyketide.

MeSH terms

  • Benzoquinones / chemistry
  • Benzoquinones / metabolism*
  • Fermentation
  • Indonesia
  • Lactams, Macrocyclic / chemistry
  • Lactams, Macrocyclic / metabolism*
  • Molecular Structure
  • Rifabutin / metabolism
  • Soil Microbiology
  • Streptomyces / metabolism*

Substances

  • Benzoquinones
  • Lactams, Macrocyclic
  • Rifabutin
  • geldanamycin