Artificial Dicopper Oxidase: Rational Reprogramming of Bacterial Metallo-beta-lactamase into a Catechol Oxidase

摘要

Development of artificial metalloenzymes has attracted much recent attention, as it provides excellent means to create advanced biocatalysts and advances our knowledge of enzymatic mechanisms. During the past decades, many strategies have been developed for the incorporation of catalytic transition-metal centers into protein matrices. These strategies can be divided into three main categories: 1) non-covalent anchoring, 2) covalent modification, and 3) dative anchoring. The first category involves the replacement of a native metal cofactor such as iron-porphyrin by a non-natural transition-metal complex and the supramolecular anchoring of a transition-metal complex using high-affinity protein-substrate interaction such as biotin-avidin interaction. The second category involves the cysteine-selective bioconjugation of artificial ligands such as bipyridine and phosphane. Dative anchoring finally uses direct coordination of transition-metal ions (dative bond) to a protein matrix to construct structural and functional mimics of more complex native enzymes.