Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of <i>An</i>VBPO from the brown seaweed <i>Ascophyllum nodosum</i> and <i>Cp</i>VBPO from the red seaweed <i>Corallina pilulifera</i>, which produce (<i>R</i>)- and (<i>S</i>)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within <i>An</i>VBPO and <i>Cp</i>VBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO₄^3- on H₂O₂-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis.