Rational design and applications of artificial metalloenzymes based on neuroglobin

Abstract

The rational design of artificial metalloenzymes enables the expansion of the functionalities of natural metalloenzymes, which has become a research hotspot in biocatalysis. As a member of the globin family, neuroglobin (Ngb) has a stable structure and possesses a tunable intramolecular disulfide bond of Cys46-Cys55, making it an ideal protein scaffold for the rational design of artificial metalloenzymes. This article systematically reviews recent progress in the rational design and applications of artificial metalloenzymes based on Ngb. It highlights strategies such as optimizing the microenvironment in the heme center, substituting key amino acid residues, constructing additional intramolecular disulfide bond, and introducing metal cofactors such as Co-porphyrin, which have successfully endowed Ngb-based artificial metalloenzymes with functions including nitrite reductase, monooxygenase, peroxidase, carbene transferase, hydrogenase, and even carbon monoxide detoxification capabilities. These advances not only deepen the understanding of the structure-function relationships of heme enzymes but also provide new insights in the rational design of artificial metalloenzymes. Artificial metalloenzymes based on Ngb and other protein scaffolds are expected to play significant roles in areas such as green synthesis, biocatalysis, environmental remediation, and biomedicine, etc.