Zeymer, C.

Protein Eng. Des. Sel. 2021, 34, 10.1093/protein/gzab003

Metalloproteins are essential to sustain life. Natural evolution optimized them for intricate structural, regulatory and catalytic functions that cannot be fulfilled by either a protein or a metal ion alone. In order to understand this synergy and the complex design principles behind the natural systems, simpler mimics were engineered from the bottom up by installing de novo metal sites in either natural or fully designed, artificial protein scaffolds. This review focuses on key challenges associated with this approach. We discuss how proteins can be equipped with binding sites that provide an optimal coordination environment for a metal cofactor of choice, which can be a single metal ion or a complex multinuclear cluster. Furthermore, we highlight recent studies in which artificial metalloproteins were engineered towards new functions, including electron transfer and catalysis. In this context, the powerful combination of de novo protein design and directed evolution is emphasized for metalloenzyme development.

Ward, T.R.

Coordination Chemistry in Protein Cages: Principles, Design, and Applications 2013, 203-219, 10.1002/9781118571811.ch8

Enzymes catalyze a wide variety of chemical reactions with high selectivity and activity under mild conditions. The research strategy in the construction of artificial metalloenzyme relies on noncovalent attachment of the metal moiety using biotin‐(strept)avidin technology. The construction of artificial metalloenzyme can be carried out by anchoring a metal moiety within a protein scaffold with the help of an anchoring group. This chapter presents the results obtained upon applying this strategy toward the generation of artificial metalloenzymes for various enantioselective transformations. The palladium‐catalyzed asymmetric allylic alkylation (AAA) is a powerful tool for the elaboration of enantiopure high‐added value compounds. The current hypothesis is that proteins with a given catalytic function are difficult to use as host for the creation of artificial metalloenzymes. Proteins which merely act as transporters (myoglobin, serum albumins, (strept)avidin, etc.) may be more suited for the creation of artificial metalloenzymes.