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

5 years ago

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

Anne-Kristin Kaster, Huijuan Guo, Christiane Weigel, John Vollmers, Z. Wilhelm de Beer, Hans-Martin Dahse, Christine Beemelmanns, Michael Poulsen, Jonathan L. Klassen, Helmar Görls, Daniel Leichnitz, Matthias Steinacker, René Benndorf

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. Gutsy research: 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 (see figure). 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701005