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 the FADH2¬ required by these enzymes. This requirement complicates biocatalysis applications since flavin reductases are not widely available, they add to the protein waste that must be removed during product isolation, and they can lead to undesired background reactions. In this study, we establish that the single component flavin reductase/flavin dependent halogenase AetF catalyzes halogenation of a diverse set of substrates. High site selectivity was observed in many cases, and activity on relatively unactivated substrates and heterocyclic substrates was demonstrated. High enantioselectivity was observed for atroposelective halogenation and halocyclization reactions. Site-selective iodination and enantioselective cycloiodoetherification was also possible using AetF. The substrate and reaction scope of AetF, along with the fact that this enzyme requires only a commercially available glucose dehydrogenase to drive its halogenase activity, suggest that it has the potential to greatly improve the utility of biocatalytic halogenation.
Supporting Information for The Single Component Flavin Reductase/Flavin Dependent Halogenase AetF is a Versatile Catalyst for Selective Bromination and Iodination of Arenes and Olefins