Chloroperoxidase halogenation

Libby RD, JA Thomas, LW Kaiser, LP Hager (1982) Chloroperoxidase halogenation reactions. J Biol Chem 257 5030-5037. 

Many chlorophenols are harmful and persistent. It is possible that these may be produced microbiologically in nature in view of the finding that a fungal chloroperoxidase halogenates phenol to yield monochlorophenols and the latter to give dichlorophenols. The sequence continues with producing trichlorophe-nols, tetrachlorophenols, and even pentachlorophenol [208]. 

Spectral similarities between P-450 and chloroperoxidase originally led to suggestions that both enzymes had thiolate ligation [20, 22, 42]. However, the two systems displayed clear differences in their catalytic activities. Furthermore, at the time when EXAFS studies of chloroperoxidase were initiated, it was not clear whether the enzyme had a free (non-disulfide linked) cysteine available to coordinate to the heme iron [100]. Also, the unusually low pH optimum of the chloroperoxidase halogenation reaction, pH 3.0 for peroxidative formation of a carbon-halogen bond [42], raised questions concerning possible protonation of the axial heme ligand(s). 

Heme-dependent haloperoxidases generate HOX as reactive species from H2O2 and X, which represents an X+ equivalent capable of undergoing electrophilic addition at electron-rich centers [270,271]. Aprototype biocatalyst of this group is the chloroperoxidase from Caldariomyces Jumago [272]. In many natural systems, such enzymes are responsible for the halogenation of electron-rich aromatic cores. 

Wannstedt, C., Rotella, D., and Siuda, J.F. Chloroperoxidase mediated halogenation of phenols. Bull. Environ. Contam. Toxicol, a 2) 282-287, 1990. 

Abbreviated proposed mechanism of vanadium chloroperoxidase-catalyzed halogenation 2123, 2124, 2146, 2172, 2173, 2175). 

Hasan Z, Renirie R, KerkmanR, Ruijssenaars HJ, Hartog AF, Wever R (2006) Laboratory-Evolved Vanadium Chloroperoxidase Exhibits 100-Fold Higher Halogenating Activity at Alkaline pH. Catalytic Effects from First and Second Coordination Sphere Mutations. J Biol Chem 281 9738... 

Longoria A, Tinoco R, Vazquez-Duhalt R (2008) Chloroperoxidase-Mediated Transformation of Highly Halogenated Monoaromatic Compounds. Chemosphere 72 485... 

Recently the amino acid sequence of vanadium chloroperoxidase was determined to have similar stretches with three families of acid phosphatases, which were previously considered unrelated [72], This sequence raises questions about the phosphatase activity of apo-V-ClPO and whether the acid phosphatases can coordinate vanadate and carry out peroxidative halogenation chemistry. In fact, apo-V-C1PO does have phosphatase activity, catalyzing the hydrolysis of/i-nitrophe-nol phosphate (p-NPP). In addition, /i-NPP displaces vanadate from V-CIPO. At this point, the haloperoxidase activity of the acid phosphatases containing coordinated vanadium(V) has not been reported. 

Hasan, Z., Renirie, R., Kerkman, R., Ruijssenaars, H.J., Hartog, A.F. and Wever, R. (2006) Laboratory-evolved vanadium chloroperoxidase Exhibits 100-fold higher halogenating activity at alkaline pH catalytic effects from first and second coordination sphere mutations. 

Horseradish peroxidase (HRP) is a hemeprotein which catalyses the oxidation of a large variety of inorganic and organic substrates (Dunford and Stillman, 1976). Chloroperoxidase (CPO) is a versatile heme enzyme since it shares similar properties with classical peroxidases and P-450 monooxygenases and also catalyses the oxidative halogenation of organic substrates (Blake and Hager, 1990). 

Itahara T, Ide N (1987) Chloroperoxidase catalyzed halogenation of pyrimidine bases. Chem Lett 12 2311-2312... 

Peroxidase transformation of mono- and dichlorinated anilines have been extensively studied, but there is scarce information about highly halogenated anilines. From several peroxidases tested, only chloroperoxidase from C.fumago was able to transform highly chlorinated anilines [69]. This first report on peroxidase transformation of pentachloroaniline showed that the main product is a polymeric material, and pentachlorophenol and tetrachloro-l,4-benzoquinone are also produced (Fig. 8.3). The mechanism of pentachlorophenol production from pentachloroaniline is still unknown. However, the tetrachloro-l,4-benzoquinone seems to be a product of the pentachlorophenol intermediate and not produced directly from the pentachloroaniline as found in pentachlorophenol peroxidase transformation [69]. The identified products from the chloroperoxidase-mediated transformation of tetrachloroaniline are the polymer, which represented 87-95% of the total mass, pentachloroaniline, and three different dimers, which have been identified as minor products [69]. 

The chloroperoxidase of C. fumago was able to transform 17 of 20 PAHs assayed [100]. In this case, only halogenated products were observed, and no oxygenated products could be detected. This biocatalytic transformation should be carefully considered because the toxicity and environmental impact of aromatic compounds may be increased. 

Chloroperoxidase Enantioselective oxidation of sulfides Enantioselective oxidation of racemic epoxyalcohols Oxidation of benzyl alcohol Epoxidation of styrene Asymmetric oxidations Halogenation reactions [11, 15,77] [15, 48] [14] [78] [79] [80]... 

Thomas JA, Morris DR, Hager LP (1970) Chloroperoxidase. VII. Classical peroxidatic, catalytic, and halogenating forms of the enzyme. J Biol Chem 245 3129-3134... 

Several enzymes that halogenate organic substrates are well known and these enzymes have been studied extensively, especially those involving alkenes, alkynes, active methylene compounds, electron-rich heterocycles (pyrroles, indoles), and phenols [1,103-105]. Both chloroperoxidase and bromoperoxidase are widespread in the... 

By definition enzymes that are able to oxidize chloride, bromide, and iodide are called chloroperoxidases and those able to oxidize bromide and iodide, bromoperoxidases. If a nucleophilic acceptor (RH) is present, a reaction will occur with HOX and halogenated compounds see Halocarbons Halocarbon Complexes) are produced (equation 2). 

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