van Pée Karl-Heinz, Patallo Eugenio P
Institut für Biochemie, TU Dresden, 01062, Dresden, Germany.
Appl Microbiol Biotechnol. 2006 May;70(6):631-41. doi: 10.1007/s00253-005-0232-2. Epub 2006 Mar 17.
The understanding of biological halogenation has increased during the last few years. While haloperoxidases were the only halogenating enzymes known until 1997, it is now clear that haloperoxidases are hardly, if at all, involved in biosynthesis of more complex halogenated compounds in microorganisms. A novel type of halogenating enzymes, flavin-dependent halogenases, has been identified as a major player in the introduction of chloride and bromide into activated organic molecules. Flavin-dependent halogenases require the activity of a flavin reductase for the production of reduced flavin, required by the actual halogenase. A number of flavin-dependent tryptophan halogenases have been investigated in some detail, and the first three-dimensional structure of a member of this enzyme subfamily, tryptophan 7-halogenase, has been elucidated. This structure suggests a mechanism involving the formation of hypohalous acid, which is used inside the enzyme for regioselective halogenation of the respective substrate. The introduction of halogen atoms into non-activated alkyl groups is catalysed by non-heme FeII alpha-ketoglutarate- and O2-dependent halogenases. Examples for the use of flavin-dependent halogenases for the formation of novel halogenated compounds in in vitro and in vivo reactions promise a bright future for the application of biological halogenation reactions.
在过去几年中，人们对生物卤化作用的理解有所增加。直到1997年，卤过氧化物酶还是唯一已知的卤化酶，但现在很清楚，卤过氧化物酶在微生物中更复杂的卤化化合物的生物合成中几乎不发挥作用（如果有作用的话）。一种新型的卤化酶，黄素依赖性卤化酶，已被确定为将氯和溴引入活化有机分子的主要参与者。黄素依赖性卤化酶需要黄素还原酶的活性来产生实际卤化酶所需的还原黄素。一些黄素依赖性色氨酸卤化酶已得到较为详细的研究，并且该酶亚家族的一个成员，色氨酸7-卤化酶的首个三维结构已被阐明。该结构表明了一种涉及次卤酸形成的机制，次卤酸在酶内部用于对相应底物进行区域选择性卤化。将卤原子引入非活化烷基是由非血红素铁IIα-酮戊二酸依赖性和O2依赖性卤化酶催化的。在体外和体内反应中使用黄素依赖性卤化酶形成新型卤化化合物的实例为生物卤化反应的应用带来了光明的前景。
