<jats:title>Abstract</jats:title><jats:p>During the search for novel natural products from entomopathogenic <jats:italic>Xenorhabdus doucetiae</jats:italic> DSM17909 and <jats:italic>X. mauleonii</jats:italic> 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 (<jats:bold>1</jats:bold>) was isolated from <jats:italic>X. mauleonii</jats:italic> DSM17908, and its structure elucidated by detailed 1 D and 2 D 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 <jats:italic>X. doucetiae</jats:italic> DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey’s analysis of <jats:bold>1</jats:bold> 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 <jats:bold>1</jats:bold> against <jats:italic>Plasmodium falciparum</jats:italic> and other neglected tropical diseases but no antibacterial activity.