Role of reduced flavin in dehalogenation reactions
Role of reduced flavin in dehalogenation reactions
复制标题
DOI：
10.1016/j.abb.2020.108696
复制
发表时间：
2021-01-15
影响因子：
3.9
通讯作者：
Sobrado，Pablo
中科院分区：
文献类型：
--
作者：
Sobrado，Pablo
卤代有机化合物广泛用于化妆品、制药和化学工业。几种天然存在的含卤素天然产物也主要由海洋生物产生。这些化合物由于其化学稳定性和缺乏生物降解途径而在环境中积累。然而，已经鉴定出一些酶在特定的生物途径中进行脱卤反应，并且已经鉴定出其他酶对卤代化合物具有次级活性。已阐明了含I、Cl、Br和F化合物的各种脱卤机理。这些机制分为还原、氧化和水解机制。黄素依赖性酶已显示出利用C4 a-氢过氧黄素中间体催化氧化脱卤反应。此外，黄素酶进行还原脱卤，形成瞬时黄素半醌。最近，黄素依赖性酶也被证明可以进行脱卤反应，其中黄素的还原形式产生共价中间体。在这里，最近的研究黄素酶在脱卤反应中的反应，重点是共价催化脱卤机制，进行了说明。
Halogenated organic compounds are extensively used in the cosmetic, pharmaceutical, and chemical industries. Several naturally occurring halogen-containing natural products are also produced, mainly by marine organisms. These compounds accumulate in the environment due to their chemical stability and lack of biological pathways for their degradation. However, a few enzymes have been identified that perform dehalogenation reactions in specific biological pathways and others have been identified to have secondary activities toward halogenated compounds. Various mechanisms for dehalogenation of I, Cl, Br, and F containing compounds have been elucidated. These have been grouped into reductive, oxidative, and hydrolytic mechanisms. Flavin-dependent enzymes have been shown to catalyze oxidative dehalogenation reactions utilizing the C4a-hydroperoxyflavin intermediate. In addition, flavoenzymes perform reductive dehalogenation, forming transient flavin semiquinones. Recently, flavin-dependent enzymes have also been shown to perform dehalogenation reactions where the reduced form of the flavin produces a covalent intermediate. Here, recent studies on the reactions of flavoenzymes in dehalogenation reactions, with a focus on covalent catalytic dehalogenation mechanisms, are described.