Artificial metalloenzymes biotin-avidin technology

Collot J, Gradinaru J, Humbert N, Skander M, Zocchi A, Ward TR. Artificial metalloenzymes for enantioselective catalysis based on biotin-avidin. J. Am. Chem. Soc. 2003 125 9030-9031. Letondor C, Humbert N, Ward TR. Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation. I roc. Natl. Acad. Sci. U.S.A. 2005 102 4683-4687. 

Thomas CM, Letondor C, Humbert N, Ward TR. Aqueous oxidation of alcohols catalyzed by artificial metalloenzymes based on the biotin-avidin technology. J. Organomet. Chem. 2005 690 4488 491. 

Artificial Metalloenzymes for Enantioselective Catalysis Based on the Biotin-Avidin Technology... 

Key words Allylic alkylation, Artificial metalloenzyme, Biotin-avidin technology, Chemogenetic optimization, Designed evolution, Enantioselective catalysis. Hybrid catalyst. Hydrogenation, Streptavidin, Transfer hydrogenation. 

We reasoned that one could mimic Nature by incorporating cofactors and metal ions to broaden the scope of accessible reactions catalyzed by protein scaffolds. Different approaches for the generation of artificial metalloenzymes have recently been reviewed [2-16]. Herein, we present the developments in the field of artificial metalloenzymes for enantioselective catalysis based on the biotin-avidin technology. The discussion includes a short introduction on the biotin-avidin technology followed by several examples of chemogenetic optimization of the performance of artificial metalloenzymes based on this technology. 

Fig. 2 Biotin-avidin technology Artificial metalloenzymes [M(L )(biotin-ligand)]c(strept)avidin for enantioselective catalysis are based on the anchoring of a catalyticaUy active metal fragment within a host protein via a hgand, a spacer, and biotin. Chemical optimization can be achieved either by varying the spacer or the metal chelate moiety ML ). Saturation mutagenesis at a position close to the metal moiety ( ) can be used for genetic optimization...

Inspired by the visionary paper of Whitesides, we adapted and extended the concept of artificial metalloenzymes (or hybrid catalysts) based on the biotin-avidin technology to enantioselective hydrogenation, transfer hydrogenation, and aUyhc alkylation reactions, which are summarized herein. 

Scheme 1 Artificial metalloenzymes based on the biotin-avidin technology for the hydrogenation of alkenes. Operating conditions used by a Whitesides [34] and b Chan [35]...

As summarized here, artificial metalloenzymes based on the biotin-avidin technology have developed into a versatile approach to enantioselective catalysis. In many cases, selectivities exceeding 92% ee could be obtained, relying on a chemogenetic optimization strategy. Such hybrid catalysts display features which are reminiscent of both homogeneous and enzymatic catalysis. 

J. Pierron, C. Malan, M. Creus, J. Gradinaru, I. Hafner, A. Ivanova, A. Sardo, T. R. Ward, Artificial metalloenzymes for asymmetric allylic alkylation on the basis of the biotin-avidin technology, Angew. them. Int. Ed., 2008, 47, 701-705. 

M. Skander, C. Malan, A. Ivanova, T. R. Ward, Chemical optimization of artificial metalloenzymes based on the biotin-avidin technology (5)-Selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers, Chem. Commun., 2005, 4815-4817. 

For a review on artificial metalloenzymes based on the biotin-avidin technology T. R. Ward, Acc. Chem. Res., 2011,44, 47. 

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