Work

Inactivation of the Burkholderia Toxin Malleicyprol by Enzymatic Cyclopropanol Ring Opening

Year: 2025

Type: article

Abstract: Pathogenic bacteria of the Burkholderia pseudomallei group cause life-threatening infections in humans and animals. Their virulence factors include malleicyprols bearing a reactive cyclopropanol moiety essential for toxicity. Inactivating this reactive motif, therefore, is a promising way to neutralize these toxins. Here, we identify a heme-dependent oxidoreductase (BurK) that cleaves the cyclopropanol warhead. Mutational analyses and in vivo radical capturing show that BurK catalyzes a radical ring opening to yield a propanone fragment. Characterizing BurK orthologs across various bacterial phyla suggests broader ecological roles of these unusual enzymes. Using a nematode model, we demonstrate that BurK-producing helper bacteria neutralize malleicyprols, significantly reducing toxicity and enhancing host survival. In addition to uncovering a novel biocatalyst, this work lays the foundation for antivirulence approaches using therapeutic microbes against antibiotic-resistant pathogens.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202521105

Authors: Jonas Fiedler, Ingrid Richter, Katharina Dornblut, Alicia Scharf, Christian Hertweck

Institutions: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI), Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Friedrich Schiller University Jena

Language: English

Topic: Burkholderia infections and melioidosis

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,510