Enzymatic Halogenases and Haloperoxidases: Computational Studies on Mechanism and Function

Despite the fact that halogenated compounds are rare in biology, a number of organisms have developed processes to utilize halogens and in recent years, a string of enzymes have been identified that selectively insert halogen atoms into, for instance, a CH aliphatic bond. Thus, a number of natural products, including antibiotics, contain halogenated functional groups. This unusual process has great relevance to the chemical industry for stereoselective and regiospecific synthesis of haloalkanes. Currently, however, industry utilizes few applications of biological haloperoxidases and halogenases, but efforts are being worked on to understand their catalytic mechanism, so that their catalytic function can be upscaled. In this review, we summarize experimental and computational studies on the catalytic mechanism of a range of haloperoxidases and halogenases with structurally very different catalytic features and cofactors. This chapter gives an overview of heme-dependent haloperoxidases, nonheme vanadium-dependent haloperoxidases, and flavin adenine dinucleotide-dependent haloperoxidases. In addition, we discuss the S-adenosyl-l-methionine fluoridase and nonheme iron/α-ketoglutarate-dependent halogenases. In particular, computational efforts have been applied extensively for several of these haloperoxidases and halogenases and have given insight into the essential structural features that enable these enzymes to perform the unusual halogen atom transfer to substrates.