卤代酶与生物卤化反应进展

Research Development on Halogenases and Biological Halogenation

卤化物在生物圈内广泛存在,许多天然卤化物广泛应用在药理学领域。根据催化机理,催化形成C-X键的卤代酶(halogenases)主要分为两大类型:卤代过氧化物酶(haloperoxidases)和黄素依赖型卤代酶(flavin-dependent halogenases),另外还有非血红素Fe(Ⅱ)/α-酮戊二酸盐依赖型卤代酶(non-heme FeⅡ/α-keto-glutarate(aKG)-dependent halogenases)、甲基卤代转移酶(methyl halide transferases)和氟化酶(fluorinases)等。本文综述了目前已知的卤代酶的发现、分子作用机制和生物催化潜力。近年来,卤代酶在生物卤化过程中的重要生物学功能已经引起了广泛关注。利用组合生物合成、定向进化等现代生物技术合成有价值的天然卤代衍生物将有广阔的应用前景。

Halogenated molecules are widely distributed in the biosphere with a variety of uses in pharmacology. Halogenating enzymes have been identified for the biosynthesis of halogenated compounds by catalyzing the formation of carbonhalogen bond. According to their different reaction mechanisms, halogenating enzymes are divided into two main groups, haloperoxidases and flavin-dependent halogenases. In addition, other halogenases including non-heine Fe^Ⅱ/α-ketoglutarate （αKG）-dependent halogenases, methyl halide transferases and fluorinase were recently discovered. This review concen- trates on the occurrence, mechanism and biocatalytic potential of the halogenating enzymes that are currently known. The biological importance of halogenating enzymes in biohalogenation has aroused wide concern. Meanwhile, using modem biotechnology, for example, combinatorial biosynthesis and directed evolution, the prospects for generating halogenated derivatives of valuable natural products would therefore appear very bright.