Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Chemical Research & Development, Pfizer Worldwide Research & Development, Groton, Connecticut 06340, USA.
Angew Chem Int Ed Engl. 2022 Dec 19;61(51):e202214610. doi: 10.1002/anie.202214610. Epub 2022 Nov 22.
Flavin-dependent halogenases (FDHs) natively catalyze selective halogenation of electron rich aromatic and enolate groups. Nearly all FDHs reported to date require a separate flavin reductase to supply them with FADH , which complicates biocatalysis applications. In this study, we establish that the single component flavin reductase/flavin dependent halogenase AetF catalyzes halogenation of a diverse set of substrates using a commercially available glucose dehydrogenase to drive its halogenase activity. High site selectivity, activity on relatively unactivated substrates, and high enantioselectivity for atroposelective bromination and bromolactonization was demonstrated. Site-selective iodination and enantioselective cycloiodoetherification was also possible using AetF. The substrate and reaction scope of AetF suggest that it has the potential to greatly improve the utility of biocatalytic halogenation.
黄素依赖卤化酶（FDHs）天然催化富电子芳香族和烯醇化物基团的选择性卤化。迄今为止报道的几乎所有 FDH 都需要单独的黄素还原酶来为它们提供 FADH，这使得生物催化应用变得复杂。在这项研究中，我们确定了单一成分黄素还原酶/黄素依赖卤化酶 AetF 使用市售的葡萄糖脱氢酶来驱动其卤化酶活性，从而催化各种底物的卤化。高位点选择性、对相对未活化底物的活性以及在手性选择性溴化和溴内酯化方面的高对映选择性得到了证明。AetF 也可用于选择性碘代和对映选择性环碘醚化。AetF 的底物和反应范围表明，它有可能极大地提高生物催化卤化的实用性。
