Repurposing Iron- and 2-Oxoglutarate-Dependent Oxygenases to Catalyze Olefin Hydration

Mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases are known to catalyze a diverse set of oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation in primary metabolism and natural product maturation. However, their use in abiotic transformations has mainly been limited to C-H oxidation. Herein, we show that various enzymes of this family, when reconstituted with Fe(II) or Fe(III), can catalyze Mukaiyama hydration-a redox neutral transformation. Distinct from the native reactions of the Fe/2OG enzymes, wherein oxygen atom transfer (OAT) catalyzed by an iron-oxo species is involved, this nonnative transformation proceeds through a hydrogen atom transfer (HAT) pathway in a 2OG-independent manner. Additionally, in contrast to conventional inorganic catalysts, wherein a dinuclear iron species is responsible for HAT, the Fe/2OG enzymes exploit a mononuclear iron center to support this reaction. Collectively, our work demonstrates that Fe/2OG enzymes have utility in catalysis beyond the current scope of catalytic oxidation. It is shown that the 2-His-1-carboxylate coordination triad commonly deployed in Fe/2OG-dependent enzymes can be used as a general ligand system to support sequential hydrogen atom transfer and oxygenation at a mononuclear iron center. This new type of reactivity not observed in nature delivered Mukaiyama hydration products of various styrene derivatives.image

Automated summary

In this study, it was discovered that mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases can catalyze diverse oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation. In addition to known reactions, these enzymes were found to catalyze the Mukaiyama hydration, which proceeds via a hydrogen atom transfer pathway without involvement of 2OG. Unlike conventional inorganic catalysts, the Fe/2OG enzymes utilize a mononuclear iron center for this reaction.