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Trottmann, Felix [Author]; Franke, Jakob [Author]; Richter, Ingrid [Author]; Ishida, Keishi [Author]; Cyrulies, Michael [Author]; Dahse, Hans-Martin [Author]; Regestein, Lars [Author]; Hertweck, Christian [Author]

Cyclopropanol Warhead in Malleicyprol Confers Virulence of Human- and Animal-Pathogenic Burkholderia Species - [published Version]

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  • Media type: Text; E-Article
  • Title: Cyclopropanol Warhead in Malleicyprol Confers Virulence of Human- and Animal-Pathogenic Burkholderia Species
  • Contributor: Trottmann, Felix [Author]; Franke, Jakob [Author]; Richter, Ingrid [Author]; Ishida, Keishi [Author]; Cyrulies, Michael [Author]; Dahse, Hans-Martin [Author]; Regestein, Lars [Author]; Hertweck, Christian [Author]
  • Published: Weinheim : Wiley-VCH Verlag, 2019
  • Published in: Angewandte Chemie - International Edition 58 (2019), Nr. 40
  • Issue: published Version
  • Language: English
  • DOI: https://doi.org/10.15488/9268; https://doi.org/10.1002/anie.201907324
  • ISSN: 1433-7851
  • Keywords: Pathogenic effects ; Animals ; Bacterial pathogens ; Metabolic profiling ; Metabolites ; Polyketide synthases ; Ketones ; natural products ; structure elucidation ; polyketides ; mass spectrometry ; virulence factors
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  • Description: Burkholderia species such as B. mallei and B. pseudomallei are bacterial pathogens causing fatal infections in humans and animals (glanders and melioidosis), yet knowledge on their virulence factors is limited. While pathogenic effects have been linked to a highly conserved gene locus (bur/mal) in the B. mallei group, the metabolite associated to the encoded polyketide synthase, burkholderic acid (syn. malleilactone), could not explain the observed phenotypes. By metabolic profiling and molecular network analyses of the model organism B. thailandensis, the primary products of the cryptic pathway were identified as unusual cyclopropanol-substituted polyketides. First, sulfomalleicyprols were identified as inactive precursors of burkholderic acid. Furthermore, a highly reactive upstream metabolite, malleicyprol, was discovered and obtained in two stabilized forms. Cell-based assays and a nematode infection model showed that the rare natural product confers cytotoxicity and virulence.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)