An Artificial Hemoprotein with Inducible Peroxidase‐ and Monooxygenase‐Like Activities

A novel inducible artificial metalloenzyme obtained by covalent attachment of a manganese(III)‐tetraphenylporphyrin (MnTPP) to the artificial bidomain repeat protein, (A3A3′)Y26C, is reported. The protein is part of the αRep family. The biohybrid was fully characterized by MALDI‐ToF mass spectrometry, circular dichroism and UV/Vis spectroscopies. The peroxidase and monooxygenase activities were evaluated on the original and modified scaffolds including those that have a) an additional imidazole, b) a specific αRep bA3‐2 that is known to induce the opening of the (A3A3′) interdomain region and c) a derivative of the αRep bA3‐2 inducer extended with a His6‐Tag (His6‐bA3‐2). Catalytic profiles are highly dependent on the presence of co‐catalysts with the best activity obtained with His6‐bA3‐2. The entire mechanism was rationalized by an integrative molecular modeling study that includes protein–ligand docking and large‐scale molecular dynamics. This constitutes the first example of an entirely artificial metalloenzyme with inducible peroxidase and monooxygenase activities, reminiscent of allosteric regulation of natural enzymatic pathways. The first example of an artificial metalloenzyme with trigger‐able oxidation activities, reminiscent of the activation or allosteric regulation of the catalytic activity of enzymes by specific regulatory proteins.