title: Structure and biosynthesis of xenoamicins from entomopathogenic Xenorhabdus.
abstract: During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 novel peptides named xenoamicins were identified in addition to the already known antibiotics xenocoumacin and xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A (1) was isolated from X. mauleonii DSM17908, and its structure elucidated by detailed 1D and 2D NMR experiments. Detailed MS experiments, also in combination with labeling experiments, confirmed the determined structure and allowed structure elucidation of additional derivatives. Moreover, the xenoamicin biosynthesis gene cluster was identified and analyzed in X. doucetiae DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey's analysis of 1 showed that the absolute configuration of the amino acids is in agreement with the predicted stereochemistry deduced from the nonribosomal peptide synthetase XabABCD. Biological testing revealed activity of 1 against Plasmodium falciparum and other neglected tropical diseases but no antibacterial activity.
authors.affiliation: Goethe-Universität Frankfurt, Department of Molecular Biotechnology, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main (Germany).
authors.forename: Qiuqin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Florian
authors.initials: F
authors.lastname: Grundmann
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiell
authors.forename: Sophie
authors.initials: S
authors.lastname: Gaudriault
authors.forename: Andreas
authors.initials: A
authors.lastname: Batzer
authors.forename: Michael
authors.initials: M
authors.lastname: Kurz
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006801:Humans; D005810:Multigene Family; D009181:Mycoses / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020593:Xenorhabdus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001688:Biological Products; D010455:Peptides
keywords: biosynthesis; natural products; peptides; structure elucidation