Title:Halogenases: A Biotechnological Alternative for the Synthesis of Halogenated Pharmaceuticals
Volume: 16
Issue: 14
Author(s): Marcela Ayala, Lorenzo Segovia and Eduardo Torres
Affiliation:
Keywords:
Biocatalysis, electrophilic biohalogenation, halogenase, halogenated pharmaceutical, nucleophilic biohalogenation.
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.