The miuraenamides, relatively simple representatives of a class of cyclodepsipeptides with high antitumor activity, can be easily and flexibly obtained by the concept of peptide modification. A reaction sequence consisting of an aldol reaction, oxidation, and methylation of the glycine subunit of the cyclodepsipeptides allows the incorporation of the unusual α,β-unsaturated dehydroamino acid in one of the last steps of the synthesis.
Simple and bioactive: 26 acyl amides have been identified in cultures of different Xenorhabdus strains and several analogues have been synthesised. Despite their simple chemical structure, several of these compounds show cytotoxicity against mammalian cell lines and insect haemocytes, thus indicating that they have a role in the complex life cycle of these bacteria.
The biosynthesis gene cluster of the xenortides and a new derivative, xenortide D, which is produced in only trace amounts, was identified in Xenorhabdus nematophila. The structure of xenortide D was elucidated using a combination of labeling experiments followed by MS analysis and was confirmed by synthesis. Bioactivity tests revealed a weak activity of tryptamine-carrying xenortides against Plasmodium falciparum and Trypanosoma brucei.
Simple urea compounds (“phurealipids”) have been identified from the
entomopathogenic bacterium Photorhabdus luminescens, and their biosynthesis was
elucidated. Very similar analogues of these compounds have been previously developed as inhibitors
of juvenile hormone epoxide hydrolase (JHEH), a key enzyme in insect development and growth.
Phurealipids also inhibit JHEH, and therefore phurealipids might contribute to bacterial
virulence.
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