Artificial metalloenzyme

[1][2] Despite fitting into classical enzyme categories, ArMs also have potential in new-to-nature chemical reactivity like catalysing Suzuki coupling,[3] metathesis[4] etc., which were never reported among natural enzymatic reactions.

ArMs have two main components: a protein scaffold and an artificial catalytic moiety, which, in this case, features a metal center.

[5] With the progress in organometallic synthesis and protein engineering, more and more new kind of design of ArMs were developed, showing promising future in both academia and industrial aspects.

[6] In 2018, one-half of the Nobel Prize in Chemistry was awarded to Frances H. Arnold "for the directed evolution of enzymes", who elegantly evolved artificial metalloenzymes to realize efficient and highly selective new-to-nature chemical reactions in vitro and in vivo.

The first attempt to anchor an abiotic metal center onto a protein was reported by Whitesides et al. using biotin-avidin interaction, making an artificial hydrogenase.

The dative anchoring strategy uses natural amino acid residue in the protein scaffold like His, Cys, Glu, Asp and Ser to coordinate to a metal center.

Like the first example of Pd-fibroin, dative anchoring to natural amino acids is not commonly used nowadays and often resulted in a more ambiguous binding site for metal compared with previous three methods.

Combining protein scaffolds featuring chelating ncAAs with different metals yields exceptionally selective artificial metalloenzymes with various application potentials.