Artificial Metalloenzymes: Challenges and Opportunities

Abstract

Artificial metalloenzymes (ArMs) result from the incorporation of an abiotic metal cofactor within a protein scaffold. From the earliest techniques of transition metals adsorbed on silk fibers, the field of ArMs has expanded dramatically over the past 60 years to encompass a range of reaction classes and inspired approaches: Assembly of the ArMs has taken multiple forms with both covalent and supramolecular anchoring strategies, while the scaffolds have been intuitively selected and evolved, repurposed, or designed in silico . Herein, we discuss some of the most prominent recent examples of ArMs to highlight the challenges and opportunities presented by the field.

Iron catalysts with N-ligands for carbene transfer of diazo reagents

“…Nevertheless, ArMs can also be obtained either by the supramolecular self-assembly or covalent anchorage of functionalized catalytic systems onto host bio-scaffolds, such as proteins or DNA (Scheme 30, pathways c and d). 91,92 It is worth noting that ArMs can also be synthesized by replacing the natural metal ion 93 with other catalytically active metals. 94,95 Artificial metalloenzymes (ArMs), 92,96,97 represent one of the most efficient and promising classes of bio-hybrid systems able to promote carbene transfer reactions in high yields, regio-and enantioselectivities.…”

Recent Advances in the Synthesis and Application of Polymer Compartments for Catalysis

“…One of the main issues in constructing a synthetic artificial system mimicking these cellular processes is the increasing compatibility problem when biocatalysts are combined with other chemocatalysts. A viable method for catalyst site isolation apart from the previous mentioned polymeric support approaches are artificial metalloenzymes that use biopolymeric materials for catalyst implementation and separation [ 168 ]. In an effort to combine the virtues of enzymes and organic metal catalysts, a cascade system was designed involving the transformation of an organometallic catalyst into an artificial metalloenzyme via host-guest chemistry without interference with enzymes [ 169 ].…”

Dynamics of Metal Complex Binding in Relation to Catalytic Activity and Selectivity of an Artificial Metalloenzyme

“…[2][3][4][5][6] A popular approach to achieve enzymatic catalysis of reactions that have no equivalent in nature involves the creation of artificial metalloenzymes, which are rationally designed hybrids of proteins with abiological catalytically active metal cofactors. [7][8][9][10][11][12][13] In this approach, the basal catalytic activity is supplied by the metal complex, whereas the second coordination sphere interactions provided by the protein scaffold are envisioned to contribute to rate acceleration and (enantio-)selectivity. Since the protein scaffolds used have not naturally evolved for the reaction of interest, usually the active site structure is far from optimal.…”