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

• Published in: Chemistry : a European journal 2017-07, Vol.23 (39), p.9338-9345
• Main Authors: Guo, Huijuan, Benndorf, René, Leichnitz, Daniel, Klassen, Jonathan L., Vollmers, John, Görls, Helmar, Steinacker, Matthias, Weigel, Christiane, Dahse, Hans‐Martin, Kaster, Anne‐Kristin, de Beer, Z. Wilhelm, Poulsen, Michael, Beemelmanns, Christine
• Format: Article
• Language: English
• Subjects: Actinomycetales - chemistry; Actinomycetales - classification; Actinomycetales - genetics; Alkaloids; Alkaloids - biosynthesis; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Assaying; Bacteria; Biosynthesis; Biosynthetic Pathways - genetics; chemical probes; Chemistry; Chromatography, High Pressure Liquid; Crystallography; Crystallography, X-Ray; drug discovery; Feeding; Fungi; Gastrointestinal tract; Gene sequencing; Genomes; Intestines - microbiology; Isoptera - microbiology; Libraries; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolites; Molecular Conformation; Multigene Family; natural products; NMR; Nuclear magnetic resonance; Phylogeny; polyketides; Secondary metabolites; Tropolone - chemistry; Whole Genome Sequencing; X-ray crystallography
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201701005

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.