黄素依赖型卤化酶及其应用研究进展

Flavin-dependent halogenases and their applications

摘要:

卤化物是农业、制药业和化学工业的重要原料，主要以化学法合成，该法具有环境不友好和合成条件苛刻等劣势。天然卤化物生物合成途径的关键酶为卤化酶，包括卤过氧化物酶(haloperoxidase，HPO)、α-酮戊二酸依赖型卤化酶(α-ketoglutarate dependent halogenase，KG-Hal)、S-腺苷甲硫氨酸依赖型卤化酶(S-adenosylmethionine-dependent halogenase)和黄素依赖型卤化酶(flavin-dependent halogenase，FDH)。其中，黄素依赖型卤化酶因其分布广泛、具有底物特异性和卤化位点选择性，是最具开发潜力的卤化酶。因此，本文对黄素依赖型卤化酶的结构、类型、催化机制及其应用研究进展进行综述，对利用基因分析和基因筛选方法寻找新型黄素依赖型卤化酶进行了展望。本综述有助于拓展黄素依赖型卤化酶的类型及其催化机制的知识，推动黄素依赖型卤化酶及其酶工程的研究，为新型卤化物的合成提供技术思路。

Abstract:

Halides are important raw materials in agriculture, pharmaceutical industry, and chemical industry. They are mainly synthesized with chemical methods which, however, cause environmental pollution and have strick requirement for the reaction conditions. The key enzymes for the biosynthesis of natural halides are halogenases, including haloperoxidase (HPO), α-ketoglutarate dependent halogenase (KG-Hal), S-adenosylmethionine-dependent halogenase, and flavin-dependent halogenase (FDH). Among them, FDHs are the most promising halogenases owing to their wide distribution, substrate specificity, and halogenated regioselectivity. Therefore, we reviewed the structures, types, catalytic mechanisms, and applications of FDHs and summarized the use of gene analysis and gene screening to search for new FDHs. This review is expected to expand the knowledge of the types and catalytic mechanisms of FDHs, boost the research on FDHs and related enzyme engineering, and provide technical ideas for the synthesis of new halides.