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

## TL;DR

Researchers discovered an enzyme called BurK that neutralizes toxic compounds from dangerous bacteria by breaking down a key reactive structure in the toxins.

## Contribution

The study identifies BurK as a novel heme-dependent oxidoreductase that inactivates malleicyprol toxins through cyclopropanol ring opening.

## Key findings

- BurK catalyzes a radical ring opening of the cyclopropanol group in malleicyprols, producing a propanone fragment.
- BurK-producing helper bacteria reduce malleicyprol toxicity and improve host survival in a nematode model.
- BurK orthologs are found across various bacterial phyla, suggesting broader ecological roles for these enzymes.

## 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.

Burkholderia pseudomallei and Burkholderia mallei are dangerous pathogens that cause severe diseases with high mortality rates. Their virulence relies in part on malleicyprols, potent toxins containing a highly reactive cyclopropanol group. In this study, we identify BurK, a heme‐dependent oxidoreductase that neutralizes malleicyprols by enzymatically opening the cyclopropanol ring.