Phintha Aisaraphon, Chaiyen Pimchai
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Wangchan Valley, Rayong, Thailand.
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Wangchan Valley, Rayong, Thailand.
J Biol Chem. 2023 Dec;299(12):105413. doi: 10.1016/j.jbc.2023.105413. Epub 2023 Nov 2.
Flavin-dependent monooxygenases (FDMOs) are known for their remarkable versatility and for their crucial roles in various biological processes and applications. Extensive research has been conducted to explore the structural and functional relationships of FDMOs. The majority of reported FDMOs utilize C4a-(hydro)peroxyflavin as a reactive intermediate to incorporate an oxygen atom into a wide range of compounds. This review discusses and analyzes recent advancements in our understanding of the structural and mechanistic features governing the enzyme functions. State-of-the-art discoveries related to common and distinct structural properties governing the catalytic versatility of the C4a-(hydro)peroxyflavin intermediate in selected FDMOs are discussed. Specifically, mechanisms of hydroxylation, dehalogenation, halogenation, and light-emitting reactions by FDMOs are highlighted. We also provide new analysis based on the structural and mechanistic features of these enzymes to gain insights into how the same intermediate can be harnessed to perform a wide variety of reactions. Challenging questions to obtain further breakthroughs in the understanding of FDMOs are also proposed.
黄素依赖单加氧酶（FDMOs）以其卓越的多功能性以及在各种生物过程和应用中的关键作用而闻名。人们已经进行了广泛的研究来探索FDMOs的结构与功能关系。大多数已报道的FDMOs利用C4a -（氢）过氧黄素作为反应中间体，将氧原子掺入多种化合物中。本综述讨论并分析了我们在理解控制酶功能的结构和机制特征方面的最新进展。讨论了与选定的FDMOs中控制C4a -（氢）过氧黄素中间体催化多功能性的常见和独特结构特性相关的最新发现。具体而言，重点介绍了FDMOs的羟基化、脱卤、卤化和发光反应机制。我们还基于这些酶的结构和机制特征提供了新的分析，以深入了解如何利用相同的中间体进行多种反应。此外，还提出了在FDMOs理解方面取得进一步突破的挑战性问题。
