Chemogenetic optimization

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. 

Results of the Chemogenetic Optimization of Artificial Metalloenzymes Based on the Biotin-Avidin Technology... 

In summary, relying on a chemogenetic optimization procedure, we have produced artificial hydrogenases based on the biotin-avidin technology for the enantioselective reduction of N-protected dehydroaminoacids [up to 96% ee (R) and 95% ee (5)] [36, 39]. Next, we outhne our recent findings in artificial aUylic... 

Fig. 9 Fingerprint display of the results for the chemogenetic optimization of the reduction of 4-bromo acetophenone and 4-phenyl-2-butanone in the presence of biotin-sepharose-immobihzed artificial transfer hydrogenases [RuH(r -arene)(Biot-VP -3)]cstreptavidin mutant [57]...

In the field of C—C bond forming reactions, palladium occupies a privileged position. In this context, the asymmetric allylic alkylation attracted our interest due to its unique outersphere attack of the malonate on the 77 -coordinated 1,3-diphenylallyl moiety. Following the above-described chemogenetic optimization procedure, we screened twenty one biotinylated ligands in conjunction with twenty two (strept)avidin isoforms for the allylic alkylation of 1,3-diphenylallyl acetate. Addition of didodecyldimethylam-... 

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. 

A. Pordea, T. R. Ward, Chemogenetic protein engineering an efficient tool for the optimization of artificial metalloenzymes, Chem. Commun., 2008, 4239-4349. 

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