Sulfoxidation mechanism of vanadium bromoperoxidase from Ascophyllum nodosum

Abstract

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...

Biocatalytic Oxidation of Primary and Secondary Alcohols

“…Most peroxidases studied to date contain ferric protoporphyrin IX as the prosthetic group and act through a high-valence iron-oxo species. [12,113] Furthermore, selenium-(glutathione peroxidase), [114] manganese-(manganese peroxidase) [115] , vanadium peroxidase- [116] and flavin-dependent peroxidases (flavoperoxidase) are known. [117] The general dilemma concerning peroxidases is that they are not only rapidly inactivated by the peroxide they depend on, but also by substrate radicals emerging during the catalytic cycle.…”

Dioxovanadium(V) Complexes of ONO Donor Ligands Derived from Pyridoxal and Hydrazides: Models of Vanadate‐Dependent Haloperoxidases

“…[5] These enzymes, and models of their active centre, catalyse the oxidation of halides by peroxide to hypohalous acid [which further halogenate non-enzymatically hydrocarbons; Equation (1)], [6] and the oxidation of organic (prochiral) sulfides to (chiral) sulfoxides. [7,8] Peroxo and hydroperoxo complexes have been proposed to act as the active intermediates. [6,9] The peroxo form, containing peroxovanadate HVO 3 (O 2 ) 2Ϫ attached to histidine, and in a tetragonal-pyramidal geometry, has been structurally characterised.…”

A new oxidovanadium(IV) Schiff base complex containing asymmetric tetradentate ONN′O′ Schiff base ligand: Synthesis, characterization, crystal structure determination, thermal study and catalytic activity

“…In 21 recent years, the coordination chemistry of Schiff base complexes of 22 oxidovanadium(IV) and dioxidovanadium(V) with N, O, and S-donor 23 chelating ligands have received considerable attention. They show 24 catalytic activity and play vital role in a variety of biochemical 25 processes such as haloperoxidation [12][13][14][15], phosphorylation [16], 26 insulin mimicking [17][18][19], nitrogen fixation [20], tumor growth 27 inhibition, and prophylaxis against carcinogenesis [17]. In addition, 28 high-valent vanadium complexes have been considered as new 29 versatile catalytic reagents for a wide range of oxidation reactions 30 [21,22], like oxidation of olefines and alcohols [23][24][25][26][27], benzene/ 31 alkylaromatic compounds [28,29], and sulfides [30][31][32] .…”