Scheme 2.

Proposed catalytic scheme for the oxidation of halide ions by VHPO enzymes (adapted from references 9 and 31a). Hydrogen peroxide in the first step reacts with the histidine-ligated vanadate center to form a vanadium–peroxo complex that reacts in the second step with a halide to give a vanadium-OX species in which X = Cl, Br, and I. VHPO enzymes are widely proposed to generate a reactive HOX species upon reacting with water to restore the vanadate active site (route A). The stereoselective Streptomyces VHPOs, like NapH1 and Mcl24, are suspected to generate an enzyme-bound halogen species (route B).