Ayala Marcela, Segovia Lorenzo, Torres Eduardo
Instituto de Biotecnología, Universidad Nacional Autónoma de México UNAM. Av. Universidad 2001 Col. Chamilpa 62210 Cuernavaca, Mor. Mexico.
Centro de Química-ICUAP, Benemerita Universidad Autonoma de Puebla BUAP. Edificio 103G CU. Col. San Manuel 72579 Puebla, Pue. Mexico.
Mini Rev Med Chem. 2016;16(14):1100-11. doi: 10.2174/1389557516666160623100619.
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.
由于小分子与蛋白质或其他生物大分子之间通过所谓的“卤键”产生的弱相互作用，卤原子在药物化合物中的作用最近得到了重新审视，这种弱相互作用可能是在大分子内特定位点结合的基础。此外，迄今为止已经描述了数千种天然卤代化合物，这表明卤原子在这些化合物中具有功能作用，以及参与这些卤代代谢物合成的多种卤化酶。在这篇小型综述中，介绍了迄今为止描述的不同卤化酶，特别是那些催化在制药领域具有潜在应用的卤化反应的酶。遵循亲电卤化机制的氧化卤化酶是最古老且特征最明确的卤化酶；然而，最近已经描述了遵循亲核卤化机制的新型卤化酶。这些酶中的一些酶的催化特性以及选择性可以通过蛋白质工程进行调节，既可以通过单点突变也可以通过定向进化；另一方面，代谢途径工程已被用于提高卤代代谢物的产量，以及生产在制药领域可能具有重要意义的新型卤代化合物。本文涵盖了酶促卤化领域的最新进展和展望。
