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.

Screening of the Antimicrobial Activity against Drug Resistant Bacteria of Photorhabdus and Xenorhabdus Associated with Entomopathogenic Nematodes from Mae Wong National Park, Thailand

“…produced isopropylstilbene that has multiple biological activities including antibiotic activity (Li et al, 1995; Buscató et al, 2013). All Xenorhabdus isolates produced xenoamicin derivatives showing weak antiprotozoal activity (Zhou et al, 2013). Additionally, we identified mevalagmapeptide (Bode et al, 2015, 2012) and the juvenile hormone epoxide hydrolase inhibitors phurealipids (Nollmann et al, 2015b) in many of the isolates.…”

Manganese(II) Semiquinonato and Manganese(III) Catecholato Complexes with Tridentate Ligand: Modeling the Substrate‐Binding State of Manganese‐Dependent Catechol Dioxygenase and Reactivity with Molecular Oxygen

“…We also applied the promoter exchange approach to X. doucetiae DSM 17909 (GenBank entry: FO704550.1) for the biosynthesis gene clusters involved in GameXPeptide (pCEP‐gxpS) and xenoamicin22 production (pCEP‐xab; Figure S5). In the latter case, the production was so good that white needles containing xenoamicin C ( 11 ) as the main compound were observed in the culture (Figure 2 D), whereas no production was visible in the non‐induced culture.…”

Defensive symbioses of animals with prokaryotic and eukaryotic microorganisms

“…; (ii) broadspectrum antibacterial and antifungal compounds, including isopropylstilbenes, 245,257,258 antraquinones, 242,259 and a carbapenem 260 from Photorhabdus spp., as well as fabclavines, 261 xenorhabdins, 262,263 xenorxides, 242 and nematophins, 245,264 from Xenorhabdus spp. ; and (iii) narrow-spectrum anti-Gram-positive xenobactin, 265 xenematide 266 and xenocoumacins, 267 and anti-Gram-negative benzylideneacetone 268 from Xenorhabdus spp. Additionally, several other metabolites including xenoamicin, 265 taxlllaids, 269 cyclohexandione, 270 chaiyaphumine 271 and szentiamide 272,273 with activity against human-disease causing protozoa (Plasmodium falciparum, Trypanosoma brucei) have been identied.…”