Artificial metalloenzymes based on protein assembly

Abstract

Metalloenzymes play essential roles in biology, whereas artificial metalloenzymes use synthetic metal cofactors for promoting non-natural reactions. In the past decades, tremendous advances have been made in manipulating artificial metalloenzymes for various organic transformation reactions, including C–H activation, C–C coupling, transfer hydrogenation, etc. Advanced methods like “Directed evolution,” “high throughput screening,” and “rational design” have stimulated the artificial metalloenzyme research. Applications of artificial metalloenzymes have been extended to cells for controlling functions like prodrug activation. Usually, for more complicated processes like multistep reactions or isolation of reaction environments, nature uses sophisticated strategies, such as positional assembly and compartmentalization of catalysts. However, artificial metalloenzyme research in this direction is relatively less. Several researchers have designed and constructed various protein assembly structures through metal coordination. However, only a few of them have been tested for catalytic activities. Assembled metalloenzymes have multiple advantages like promoting multistep reactions, stabilizing the catalyst, cooperativity in the reaction, higher-order complexity, sophisticated structures, confinement of reaction, etc. Therefore, systematic investigations on their design, structure, and activity are necessary to represent them as next-generation biocatalysts. In this context, the current review highlights the importance of self-assembled metalloenzymes, available design strategies, current developments, catalytic activities, and the future direction of the research.