Haloperoxidases enzymatic halogenation

Jumago, are easily obtained. Chloroperoxidase can also be obtained in larger quantities from the fungus Curvularia inaequalisi40K Thus, a number of different haloperoxidases from various sources are available in quantities necessary for the enzymatic halogenation of organic compounds. 

Enzymatic halogenation catalyzed by haloperoxidases and perhydrolases involves the oxidation of halide ions to a halonium ion species which leads to the formation of hypohalous acids (Fig. 16.9-1). The products obtained by enzymatic halogenation with these enzymes are the same as the products obtained by chemical electrophilic halogenation with hypohalous acids. The differences in the para ortho ratios in the halogenation of some aromatic compounds could be due to a mixture of halogenation at or near the active site and in solution. 

The major advantage of enzymatic halogenation using haloperoxidases and perhydrolases is that the enzymes have a very low substrate specificity and that no free halogen is needed which makes halogenation catalyzed by these enzymes less hazardous than chemical halogenation. 

In view of the predominant chemical nature of biohalogenation, it seems that enzymatic halogenation reactions involving haloperoxidase enzymes do not show... 

A striking array of halogenated products produced by natural sources is found in the biosphere. The majority are probably formed by the enzymatic activity of haloperoxidases. The detailed mechanism by which haloperoxidases catalyze the insertions of a halogen into organic molecules is still a point of debate. However, for most of these enzymes a simple reaction mechanism has been observed that consists of a two-electron oxidation of the electron donor (Cl", Br", I") by H2O2 to hypohalous acids (equation 1) ... 

In contrast to FADH2-dependent halogenases, haloperoxidases have no substrate specificity. The enzymatic iodination, bromination, and chlorination of a number of different aromatic compounds by haloperoxidases have been reported in the last few years. All aromatic substrates halogenated successfully by haloperoxidases are aromatic compounds activated for electrophilic substitution (Table 16.9-1). 

Unfortunately, direct epoxidation of alkenes by metal-free haloperoxidases led to racemic epoxides [1331, 1332]. Since the reaction only takes place in the presence of a short-chain carboxylic acid (e.g., acetate or propionate), it is believed to proceed via an enzymatically generated peroxycarboxylic acid, which subsequently oxidizes the alkene without the aid of the enzyme. This mechanism has a close analogy to the lipase-catalyzed epoxidation of alkenes (Sect 3.1.5) and halogenation reactions catalyzed by haloperoxidases (Sect. 2.7.1), where enzyme catalysis is only involved in the formation of a reactive intermediate, which in turn converts the substrate in a spontaneous (nonenzymatic) foUowup reaction. 

Haloperoxidases have been shown to transform alkenes by a formal addition of hypohalous acid to produce halohydrins. The reaction mechanism of enzymatic halogenatitHi has been debated for some time and it is now accepted that it proceeds via a halonium intermediate [1770, 1771], similar to the chemical formation of halohydrins (Scheme 2.228). The former species is derived from hypohalous acid or molecular halogen, which is in turn produced by the enzyme via oxidation of halide [1772]. In support of this, a HOCl-adduct of Fe -protoporphyrin IX was identified as a direct enzyme-halogen intermediate involved in chloroperoxidase-catalyzed halogenaticHi [1773]. 

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