Haloperoxidases

Haloperoxidases are a class of enzymes that catalyze the oxidation of halide ions (chloride, bromide, iodide) by hydrogen peroxide to generate reactive halogenating species, most commonly hypohalous acids such as HOCl, HOBr, and HOI. These species can directly halogenate organic substrates or participate in subsequent reactions that lead to halogenated products.

Two major families exist: heme-containing haloperoxidases, including chloroperoxidase from Caldariomyces fumago, and the larger group of vanadium-dependent haloperoxidases (V-HPOs) found in various marine organisms. The two groups differ in their metal cofactor and catalytic mechanism: chloroperoxidase uses a heme cofactor to activate H2O2, whereas V-HPOs employ a vanadium(V) center as part of their active site to generate hypohalospecies.

Mechanistically, the enzyme first reacts with hydrogen peroxide to form a reactive intermediate that oxidizes the halide ion to a hypohalite species. The resulting HOX can then halogenate substrates or release to effect non-enzymatic halogenation steps in the surrounding medium. Substrate scope includes chloride, bromide, and iodide, with selectivity influenced by enzyme type and conditions. CPO and V-HPOs can catalyze chlorination, bromination, and iodination reactions under mild conditions.

Haloperoxidases occur in fungi, algae, and some bacteria. In nature they contribute to the biosynthesis of halogenated natural products and to chemical defense, and they participate in the formation of extracellular halogenated metabolites in marine ecosystems.

Due to their ability to perform regio- and chemoselective halogenation under mild conditions, haloperoxidases are studied for biocatalysis and synthesis of halogenated compounds, and have potential applications in environmental remediation and analytical chemistry.