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Site-selective chlorination of pyrrolic heterocycles by flavin dependent enzyme PrnC
Communications Chemistry ( IF 5.9 ) Pub Date : 2024-01-05 , DOI: 10.1038/s42004-023-01083-1
GuangRong Peh 1 , Terence Tay 2 , Lee Ling Tan 3 , Elaine Tiong 3 , Jiawu Bi 3 , Yi Ling Goh 1 , Suming Ye 1 , Fu Lin 2 , Cheryl Jia Xin Tan 4 , Yong Zi Tan 3, 4, 5 , Joel Wong 1 , Huimin Zhao 2, 6 , Fong Tian Wong 1, 3 , Ee Lui Ang 2, 7 , Yee Hwee Lim 1, 7
Affiliation  

Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil.



中文翻译:


黄素依赖性酶 PrnC 对吡咯杂环进行位点选择性氯化



吡咯的卤化需要强亲电试剂,并且常常会产生不需要的多卤化产物。鉴于其化学选择性和良好的反应条件,生物催化卤化是一种非常有吸引力的方法。虽然有机合成中酶法苯酚和吲哚卤化已有一些报道,但缺乏酶法吡咯卤化的相应报道。在这里,我们描述了 PrnC 的体外功能和结构特征,PrnC 是一种黄素依赖性卤化酶,可以作用于独立的吡咯。计算模型和位点诱变研究确定了催化口袋中的三个关键残基。使用单粒子低温电子显微镜的中等分辨率图显示 PrnC 是二聚体。这种天然的 PrnC 可以以位点选择性的方式卤化结构多样的吡咯杂环文库,并应用于农用化学杀菌剂咯菌腈的氯化类似物的化学酶合成。

更新日期:2024-01-06
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