Engineering Artificial Metalloenzymes

Genetically Encoded Phosphine Ligand for Metalloprotein Design

“…To bridge the large gap between the nonbiological phosphine ligands and protein chemistry, scientists have successfully inserted phosphine ligands and their metal complexes into proteins in vitro and created new artificial metalloenzymes (ArMs); this was achieved through covalently modifying protein side-chains or by utilizing noncovalent binding via high-affinity anchors (Figure C) . ArMs are remarkable hybrid catalysts that merge the superior molecular recognition of protein scaffolds with the unique and versatile reactivity of transition-metal or organo-catalysts invented by humans . However, due to the oxygen sensitivity of phosphine ligands, researchers have mainly constructed ArMs by directly conjugating preexisting phosphine-transition metal catalysts with proteins, and this strategy dates back to Wilson and Whitesides’ initial incorporation of a biotinylated phosphine-rhodium catalyst into the avidin scaffold in 1978 .…”