The benzodiazepine-like natural product tilivalline is produced by the entomopathogenic bacterium Xenorhabdus eapokensis

PLoS One. 2018 Mar 29;13(3):e0194297. doi: 10.1371/journal.pone.0194297. eCollection 2018.

Abstract

The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated hemorrhagic colitis. Here we show the identification of tilivalline and analogs thereof in the entomopathogenic bacterium Xenorhabdus eapokensis as well as the identification of its biosynthesis gene cluster encoding a bimodular non-ribosomal peptide synthetase. Heterologous expression of both genes in E. coli resulted in the production of 1 and from mutasynthesis and precursor directed biosynthesis 11 new tilivalline analogs were identified in X. eapokensis. These results allowed the prediction of the tilivalline biosynthesis being similar to that in K. oxytoca.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodiazepinones / chemistry
  • Benzodiazepinones / metabolism*
  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Chromatography, High Pressure Liquid
  • Enterobacteriaceae / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genes, Bacterial
  • Molecular Structure
  • Multigene Family
  • Tandem Mass Spectrometry

Substances

  • Benzodiazepinones
  • Biological Products
  • tilivalline

Grants and funding

This work was supported by a Starting grant from the European Research Council (grant agreement number 311477) and Deutsche Forschungsgemeinschaft INST 161/810-1 to Dr. Helge B. Bode. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.