title: Halogenases: A Biotechnological Alternative for the Synthesis of Halogenated Pharmaceuticals.
abstract: The role of halogen atoms in pharmaceutical compounds has been recently revised, due to the weak interaction through the so called "halogen bond" between small molecules and proteins or other biomacromolecules, which could be fundamental for binding at a particular site within the macromolecule. Moreover, thousands of natural halogenated compounds have been described to date, pointing to a functional role of halogen atoms in these compounds, as well as a diversity of halogenating enzymes involved in the synthesis of these halogenated metabolites. In this mini-review the different halogenases described to date are presented, particularly those catalyzing halogenation reactions with potential applications in the pharmaceutical field. Oxidative halogenases following an electrophilic halogenation mechanism are the oldest and best characterized halogenases; however, novel halogenases following a nucleophilic halogenation mechanism have been recently described. The catalytic properties as well as the selectivity of some of these enzymes can be modulated through protein engineering, both by single point mutations or by directed evolution; on the other hand, metabolic pathway engineering has been used to improve the production of halogenated metabolites, as well as to produce novel halogenated compounds, potentially important in the pharmaceutical field. Recent advances and prospective on the field of enzymatic halogenation are covered.
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México UNAM. Av. Universidad 2001 Col. Chamilpa 62210 Cuernavaca, Mor. Mexico. maa@ibt.unam.mx.
authors.forename: Marcela
authors.initials: M
authors.lastname: Ayala
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Segovia
authors.affiliation: Centro de Química-ICUAP, Benemerita Universidad Autonoma de Puebla BUAP. Edificio 103G CU. Col. San Manuel 72579 Puebla, Pue. Mexico. eduardo.torres@correo.buap.mx.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Torres
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology; D055162:Biocatalysis; D001709:Biotechnology / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002711:Chloride Peroxidase / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D054879:Halogenation; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D002711:Chloride Peroxidase; D006867:Hydrolases; C046137:haloalkane dehalogenase