C. fumagoChloroperoxidase is also a Dehaloperoxidase:  Oxidative Dehalogenation of Halophenols

Abstract

We have examined the H2O2-dependent oxidative dehalogenation of 2,4,6-trihalophenols and p-halophenols catalyzed by Caldariomyces fumago chloroperoxidase (CCPO). CCPO is significantly more robust than other peroxidases and can function under harsher reaction conditions, and so its ability to dehalogenate halophenols could lead to its use as a bioremediation catalyst for aromatic dehalogenation reactions. Optimal catalysis occurred under acidic conditions (100 mM potassium phosphate solution, pH 3.0). UV-visible absorption spectroscopy, high-performance liquid chromatography, and gas chromatography/mass spectrometry clearly identified the oxidized reaction product for CCPO-catalyzed dehalogenation of 2,4,6-trihalophenols as the corresponding 2,6-dihalo-1,4-benzoquinones. This reaction has previously been reported for two His-ligated heme-containing peroxidases (see Osborne, R. L.; Taylor, L. O.; Han, K. P.; Ely, B.; Dawson, J. H. Biochem. Biophys. Res. Commun. 2004, 324, 1194-1198), but this is the first example of a Cys-ligated heme-containing peroxidase functioning as a dehaloperoxidase. The relative catalytic efficiency (turnover number) of CCPO reported herein is comparable to that of horseradish peroxidase (Ferrari, R. P.; Laurenti, E.; Trotta, F. J. Biol. Inorg. Chem. 1965, 4, 232-237). The mechanism of dehalogenation has been probed using p-halophenols as substrates. Here the major product is a dimer with 1,4-benzoquinone as the minor product. An electron-transfer mechanism is proposed that accounts for the products formed from both the 2,4,6-trihalo- and p-halophenols. Finally, we note that this is the first case of a peroxidase known primarily for its halogenation ability being shown to also dehalogenate substrates.

Characterization of Recombinant Chloroperoxidase, and F103A and C29H/C79H/C87H Mutants

“…Chloroperoxidase can catalyze many reactions that are important in synthesis such as sulfoxidation (Silverstein and Hager 1974;Doerge 1986), hydroxylation (Miller, Tschirret-Guth et al 1995) and epoxidation (Geigert, Lee et al 1986), enantioselectivly and in high yield (Casella, Poli et al 1994;Lakner and Hager 1996), such as the epoxidation of olefins (Ortiz de Montellano, Choe et al 1987), where traditional peroxidases have failed. Other reactions such as N-demethylation (Kedderis, Koop et al 1980) and dehalogenation (Osborne, Raner et al 2006) are also possible.…”

Nuclear Magnetic Resonance Spectroscopic and Computational Investigations of Chloroperoxidase Catalyzed Regio- and Enantio-Selective Transformations

“…Contrary to its primary biological function chlorination, CPO can dehalogenate substrates [39] such as trihalophenols, p-halophenols, and 4-fluorophenol, which may have important environmental implications. Additionally, CPO is able to transform tetra-and penta-chlorinated phenols and anilines, which are widely distributed pollutants [61].…”

“…CPO is able to catalyze a wide variety of reactions including halogenation [28,29,30], oxidation [31,32,33,34,35,36], N-demethylation [37,38], dehalogenation [39,40], and dismutation reactions [31] (see Figure 1.6). Significantly, the epoxidation and sulfoxidation reactions catalyzed by CPO are highly enantioselective [41,42,43,44,45,46,47], which suggests a potential application in pharmaceutical industry.…”

“…Chloroperoxidase (CPO), a heme-thiolate protein secreted by the marine fungus Caldariomyces fumago [23], is a versatile enzyme [25] capable of catalyzing a broad spectrum of chemical reactions including halogenation [28], dehalogenation [39], N-demethylation [37], dismutation [23], epoxidation [42], and oxidation [34,41,129,130,131]. Therefore, CPO has been the subject of numerous biotechnological investigations due to its potential applications in synthetic chemistry as well as pharmaceutical industry [44,46,132,133].…”

“…Chloroperoxidase (CPO) itself catalyzes a broad class of reactions including halogenation [28], dehalogenation [39], N-demethylation [37], epoxidation of alkenes [42], dismutation of peroxide [31], and oxidation of organic compounds such as sulfides [197], alcohols [34], and amines [130]. A remarkable feature of CPO is to catalyze oxygen insertions with a high enantioselectivity in sulfoxidation [41,198] and epoxidation reactions [42,43], which offers a great potential in the synthesis of chiral compounds [46,109,133].…”