Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA.
Nat Commun. 2019 Mar 19;10(1):1255. doi: 10.1038/s41467-019-09215-9.
Controlled halogenation of chemically versatile substrates is difficult to achieve. Here we describe a unique flavin-dependent halogenase, PltM, which is capable of utilizing a wide range of halides for installation on a diverse array of phenolic compounds, including FDA-approved drugs and natural products, such as terbutaline, fenoterol, resveratrol, and catechin. Crystal structures of PltM in complex with phloroglucinol and FAD in different states yield insight into substrate recognition and the FAD recycling mechanism of this halogenase.
化学多功能底物的可控卤化难以实现。在这里，我们描述了一种独特的黄素依赖卤化酶 PltM，它能够利用各种卤化物将其安装在各种酚类化合物上，包括 FDA 批准的药物和天然产物，如特布他林、非诺特罗、白藜芦醇和儿茶素。PltM 与根皮素和不同状态下的 FAD 复合物的晶体结构提供了对该卤化酶的底物识别和 FAD 循环机制的深入了解。
