Guo, HuijuanBenndorf, ReneLeichnitz, DanielKlassen, Jonathan L.Vollmers, JohnGoerls, HelmarSteinacker, MatthiasWeigel, ChristianeDahse, Hans-MartinKaster, Anne-KristinPoulsen, MichaelBeemelmanns, Christine2017-08-142017-07Guo, H.J., Benndorf, R., Leichnitz, D., Klassen, J.L., Vollmers, J., Gorls, H., Steinacker, M., Weigel, C., Dahse, H.M., Kaster, A.K., De Beer, Z.W., Poulsen, M. & Beemelmanns, C. 2017, 'Isolation, biosynthesis and chemical modifications of rubterolones A-F : rare tropolone alkaloids from Actinomadura sp. 5-2', Chemistry : A European Journal, vol. 23, no. 39, 9338-9345.1521-3765 (online)0947-6539 (print)10.1002/chem.201701005http://hdl.handle.net/2263/61635The 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.en© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the pre-peer reviewed version of the following article : 'Isolation, biosynthesis and chemical modifications of rubterolones A-F : rare tropolone alkaloids from Actinomadura sp. 5-2', Chemistry : A European Journal, vol. 23, no. 39, 9338-9345., 2017, doi : 10.1002/chem.201701005. The definite version is available at : http://onlinelibrary.wiley.comjournal/10.1002/(ISSN)1521-3765.BiosynthesisPolyketidesNatural productsDrug discoveryChemical probesPostprint Article