参与抗生素生物合成的FADH_2依赖型卤化酶研究进展

Recent developments of FADH_2-dependent halogenases involved in the biosynthesis of antibiotics

从发现第一个天然卤化物到现在已有100多年了。在已发现的约4500个天然卤化物中有很多在医药等领域应用广泛,其中包括许多重要的抗生素。直到19世纪90年代中期,人们一直认为生物卤化反应主要由卤过氧化物酶负责催化。近期在许多关于抗生素生物合成基因簇的研究中发现FADH2依赖型卤化酶催化的卤化反应才是许多微生物及其它生物中的主要卤化机制。本文综述了参与抗生素生物合成的FADH2依赖型卤化酶的发现,催化机制及各种来源的该类卤化酶研究进展,并介绍了该类酶在组合生物合成及寻找天然卤化物等方面的应用。

The existence of halogenated nature compounds has been known for over 100 years and nearly 4,500 of them have been identified so far. Many of these compounds are used widely in medicine, such as some important antibiotics. It was largely accepted that most biological halogenation reactions were catalyzed by haloperoxidase until the middle of 1990s. Recent researches on the biosynthesis gene clusters of antibiotics revealed that FADH2-dependent halogenases play a prominent role in enzymatic halogenations. This review will introduce the detection, reaction mechanism, distribution and application of FADH2-dependent halogenases.