Rational Design of Artificial Metalloenzymes: Case Studies in Myoglobin

Metalloenzymes play diverse important functions in biological systems. Meanwhile, design of artificial metalloenzymes may fine-tune and expand the functionalities of natural metalloenzymes, and even create novel enzymes with more advanced functions. Myoglobin (Mb) is an ideal protein model for design of heme proteins and other metalloenzymes. In recent years, various approaches have been developed for design of artificial metalloenzymes based on the protein scaffold of Mb, which include design of hydrogen-bonding network, intramolecular disulfide bond, the use of post-translational modifications, introduction of non-natural amino acids and non-native cofactors. This review summaries the recent progress in these aspects, which will help us understand the structure and function relationship of metalloenzymes, master the idea and methodologies of artificial metalloenzyme design, thereby promoting the rapid development in this field.