Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypohalous acid. We demonstrate that these enzymes also slowly mediate the enantioselective oxidation of organic sulfides (methyl phenyl sulfide, methyl p-tolyl sulfide, and 1-methoxy-4 (methylthio)benzene) to the corresponding sulfoxides (turnover frequency 1 min(-)(1)). The vanadium bromoperoxidase from the brown seaweed Ascophyllum nodosum converts methyl phenyl sulfide to the (R)-enantiomer of the sulfoxide (55% yield and 85% enantiomeric excess (ee)). At low peroxide concentrations a selectivity of 91% can be attained. The enzyme catalyzes the selective sulfoxidation reaction over a broad pH range with an optimum around pH 5-6 and remains completely functional during the reaction. When the vanadium bromoperoxidase from the red seaweed Corallina pilulifera is used the (S)-enantiomer (18% yield and 55% ee) is formed. In contrast, the vanadium chloroperoxidase from the fungus Curvularia inaequalis catalyzes the production of a racemic mixture (54% yield), which seems to be an intrinsic characteristic of this enzyme.

We have previously shown that vanadium bromoperoxidase from Ascophyllum nodosum mediates production of the (R)-enantiomer of methyl phenyl sulfoxide with 91% enantiomeric excess. Investigation of the intrinsic selectivity of vanadium bromoperoxidase reveals that the enzyme catalyzes the sulfoxidation of methyl phenyl sulfide in a purely enantioselective manner. The K m of the enzyme for methyl phenyl sulfide was determined to be < 3.5 mm in the presence of 25% methanol or tert-butanol. The selectivity of the sulfoxidation of methyl phenyl sulfide is optimal in the temperature range 25±30 8C and can be further optimized by increasing the enzyme concentration, yielding selectivities with up to 96% enantiomeric excess. Furthermore, we established for the first time that vanadium bromoperoxidase is functional at temperatures up to 70 8C. A detailed investigation of the sulfoxidation activity of this enzyme using 18 O-labeled hydrogen peroxide shows that vanadium bromoperoxidase mediates the direct transfer of the peroxide oxygen to the sulfide. A schematic model of the vanadium haloperoxidase sulfoxidation mechanism is presented.Keywords: enantioselective sulfoxidation; selective oxygen-transfer; vanadium bromoperoxidase; vanadium chloroperoxidase.In response to scientific and pharmaceutical interest in enantiomerically pure sulfoxides a number of catalytic methods for the production of these chiral synthons has been developed [1,2]. Several different methods for the preparation of chiral sulfoxides by enantioselective oxidation of the corresponding organic sulfides exist using chemical [3] and biological, whole-cell [4] and enzymatic [5,6] approaches. Inorganic vanadium (V) peroxo-complexes, some of which have been suggested to be functional models for the vanadium peroxidases [7], mediate oxygen-transfer reactions to a variety of organic compounds including sulfides [8]. Several chiral Schiff-baseligated vanadium (V) peroxo-complexes catalyze the formation of optically active sulfoxides, with selectivities up to 78% enantiomeric excess [9,10]. It was recently demonstrated that the vanadium haloperoxidases are also capable of mediating selective sulfoxidation reactions in the presence of hydrogen peroxide [11±13]. Vanadium bromoperoxidase (VBPO) from the brown seaweed Ascophyllum nodosum promotes formation of the (R)-enantiomer of the methyl phenyl sulfoxide with 91% enantiomeric excess under optimal reaction conditions, whereas VBPO from the red seaweed Corallina pilulifera mediates formation of the (S)-enantiomer (55% enantiomeric excess). Recombinant vanadium chloroperoxidase (VCPO), however, produces a racemic mixture of the sulfoxides, which appeared to be an intrinsic characteristic of the enzyme. In addition, it has been reported [13,14] that VBPO from the red seaweed C. officinalis catalyzes the selective sulfoxidation of small aromatic sulfides and small sulfides possessing a cis-positioned carboxyl group to the (S)-enantiomer of the corresponding sulfoxides with selectivities exceeding 95% enantiomeric ex...

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