Cyclopropanol Warhead in Malleicyprol Confers Virulence of Human- and Animal-Pathogenic Burkholderia Species.

Abstract:

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.

SEEK ID: https://data.chembiosys.de/publications/152

PubMed ID: 31353766

Projects: B1, Z02

Publication type: Journal

Journal: Angew Chem Int Ed Engl

Citation: Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14129-14133. doi: 10.1002/anie.201907324. Epub 2019 Aug 27.

Date Published: 1st Oct 2019

Registered Mode: by PubMed ID

Authors: F. Trottmann, J. Franke, I. Richter, K. Ishida, M. Cyrulies, H. M. Dahse, L. Regestein, C. Hertweck

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Created: 24th Nov 2021 at 12:14

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