title: Characterisation of taxlllaids A-G; natural products from Xenorhabdus indica.
abstract: Six new lipodepsipeptides and an additional linear derivative named taxlllaids A-G (1-7) have been identified in the entomopathogenic bacterium Xenorhabdus indica. The structures of the main compounds have been solved by detailed NMR spectroscopic analysis and the structures of minor derivatives were elucidated by a combination of labelling experiments and detailed MS experiments. The absolute configuration of the taxlllaids was deduced by using the advanced Marfey method and analysis of the biosynthesis gene cluster showing the presence of epimerisation domains, which was subsequently proved to be correct by solid-phase peptide synthesis of all taxlllaids. The exchange of a single amino acid in the adenylation domain was shown to be responsible for substrate promiscuity of the third A domain, resulting in the incorporation of leucine, phenylalanine or tyrosine. Bioactivity testing revealed the taxlllaids to be weakly active against Plasmodium falciparum and against a number of eukaryotic cell lines.
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Johann Wolfgang Goethe-Universität Frankfurt am Main, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main (Germany), Fax: (+49) 69-798-29527.
authors.forename: Max
authors.initials: M
authors.lastname: Kronenwerth
authors.forename: Kenan A J
authors.initials: KA
authors.lastname: Bozhüyük
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Kahnt
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Sophie
authors.initials: S
authors.lastname: Gaudriault
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D007930:Leucine / Q000138:chemical synthesis* / Q000737:chemistry*; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010649:Phenylalanine / Q000138:chemical synthesis* / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D020593:Xenorhabdus / Q000737:chemistry*
chemical_list: D001688:Biological Products; D055666:Lipopeptides; D010649:Phenylalanine; D007930:Leucine
keywords: biosynthesis; isotopic labeling; mass spectrometry; natural products; peptides