Metalloenzyme design and engineering through strategic modifications of native protein scaffolds

Metalloenzymes are among the major targets of protein design and engineering efforts aimed at attaining novel and efficient catalysis for biochemical transformation and biomedical applications, due to the diversity of functions imparted by the metallo-cofactors along with the versatility of the protein environment. Naturally evolved protein scaffolds can often serve as robust foundations for sustaining artificial active sites constructed by rational design, directed evolution, or a combination of the two strategies. Accumulated knowledge of structure-function relationship and advancement of tools such as computational algorithms and unnatural amino acids incorporation all contribute to the design of better metalloenzymes with catalytic properties approaching the needs of practical applications.