Structure and Biosynthesis of Xenoamicins from Entomopathogenic Xenorhabdus

Qiuqin Zhou (1) , Florian Grundmann (1) , Marcel Kaiser (2) , Matthias Schiell (3) , Sophie Gaudriault (4) , Andreas Batzer (3) , Michael Kurz (3) , Helge B. Bode (1)

1 Department of Molecular Biotechnology
2 STI - Institut Tropical et de Santé Publique Suisse
3 R&D
4 DGIMI - Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier]

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 xenoamicinA (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.

Mots clés: biosynthesis; natural products; peptides; structure elucidation

Mots clés: xenorhabdus; biosynthèse; peptide

Domaines: Sciences du Vivant [q-bio]

Qiuqin Zhou, Florian Grundmann, Marcel Kaiser, Matthias Schiell, Sophie Gaudriault, et al.. Structure and Biosynthesis of Xenoamicins from Entomopathogenic Xenorhabdus. Chemistry - A European Journal, 2013, 19 (49), pp.16772-16779. ⟨10.1002/chem.201302481⟩. ⟨hal-01837255⟩