Recent advances in the field of artificial hemoproteins: New efficient eco-compatible biocatalysts for nitrene- oxene- and carbene-transfer reactions

In the last few years, the field of artificial hemoproteins has been expanding through two main strategies involving either the incorporation of synthetic metalloporphyrin derivatives into the chiral cavity of a protein or the directed evolution of natural hemoproteins such as myoglobin and cytochromes P450. First, various synthetic water-soluble porphyrins including ions of transition metals such as iron and manganese have been inserted covalently or by supramolecular anchoring into non-specifically designed native proteins or into proteins modified by a minimum number of mutations. The obtained artificial hemoproteins were able to catalyze oxene transfer reactions such as epoxidation of alkenes or sulfoxidation of sulfides and cyclopropanation reactions with good activities and moderate enantioselectivities. Recently, a second approach, based on the design of the active site of already existing native hemoproteins such as myoglobin and cytochromes P450 by directed evolution, has led to new artificial hemoproteins that are able to catalyze oxene transfer reactions with improved activities as well as with abiological reactions. This approach thus provided promising tools for the catalysis of reactions such as intramolecular or intermolecular carbene and nitrene transfer reactions with high efficiencies. In addition, in all cases, after a few rounds of mutagenesis, mutants that were able to catalyze those reactions with a high enantioselectivity could be obtained. Finally, several groups showed that these new artificial metalloenzymes could also be used for the preparative scale-production of compounds with an excellent enantioselectivity, opening new pathways for the industrial synthesis of compounds of pharmaceutical interest.