Inactivation of the Burkholderia Toxin Malleicyprol by Enzymatic Cyclopropanol Ring Opening.

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 an

SUBMITTER: Fiedler J 

PROVIDER: S-EPMC12790350 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature