Isolation, Biosynthesis and Chemical Modifications of Rubterolones A-F: Rare Tropolone Alkaloids from Actinomadura sp. 5-2

Chemistry. 2017 Jul 12;23(39):9338-9345. doi: 10.1002/chem.201701005. Epub 2017 Jun 21.


The discovery of six new, highly substituted tropolone alkaloids, rubterolones A-F, from Actinomadura sp. 5-2, isolated from the gut of the fungus-growing termite Macrotermes natalensis is reported. Rubterolones were identified by using fungus-bacteria challenge assays and a HRMS-based dereplication strategy, and characterised by NMR and HRMS analyses and by X-ray crystallography. Feeding experiments and subsequent chemical derivatisation led to a first library of rubterolone derivatives (A-L). Genome sequencing and comparative analyses revealed their putative biosynthetic pathway, which was supported by feeding experiments. This study highlights how gut microbes can present a prolific source of secondary metabolites.

Keywords: biosynthesis; chemical probes; drug discovery; natural products; polyketides.

MeSH terms

  • Actinomycetales / chemistry*
  • Actinomycetales / classification
  • Actinomycetales / genetics
  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology
  • Animals
  • Biosynthetic Pathways / genetics
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Intestines / microbiology
  • Isoptera / microbiology
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Conformation
  • Multigene Family
  • Phylogeny
  • Tropolone / chemistry*
  • Whole Genome Sequencing


  • Alkaloids
  • Tropolone