Natural, Designed and Engineered Metalloenzymes: Structure, Catalytic Mechanisms and Applications

Bioinorganic chemists have become engaged in the challenge of elucidating the molecular mechanisms that govern how protein scaffolds modulate the properties of metal cofactors. One of the most powerful tools for this purpose consists of the construction of model systems replicating the structural and functional features of their natural counterparts. Metalloenzymes also represent a significant source of inspiration: Researchers have attempted for decades to construct efficient and selective catalysts by engineering metal binding sites into natural or de-novo-designed protein scaffolds. From this perspective, the construction of artificial metalloenzymes goes beyond the goal of elucidating the catalytic mechanism of natural biocatalysts and aims to manipulate or improve their catalytic properties into tailor-made systems. This Special Issue of the International Journal of Molecular Sciences has collated some recent contributions involving the development of artificial metalloenzymes for challenging biocatalytic applications. Several strategies have been successfully applied to this purpose, and some prominent examples are reported herein.