The incorporation of a synthetic, catalytically competent metallo cofactor into a protein scaffold to generate an artificial metalloenzyme (ArM) lead to new activities specific of the cofactor. Here NHC= N-heterocyclic carbenes Grubs-type catalyst with organophosphate function, inhibits cutinase and forms an artificial metalloenzyme for olefin metathesis
A series of Grubbs-type catalysts that contain lipase-inhibiting phosphoester functionalities have been synthesized and reacted with the lipase cutinase, which leads to artificial metalloenzymes for olefin metathesis. The resulting hybrids comprise the organometallic fragment that is covalently bound to the active amino acid residue of the enzyme host in an orthogonal orientation. Differences in reactivity as well as accessibility of the active site by the functionalized inhibitor became evident through variation of the anchoring motif and substituents on the N-heterocyclic carbene ligand. Such observations led to the design of a hybrid that is active in the ring-closing metathesis and the cross-metathesis of N,N-diallyl-p-toluenesulfonamide and allylbenzene, respectively, the latter being the first example of its kind in the field of artificial metalloenzymes.
