title: Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation.
abstract: Most physiological and biotechnological processes rely on molecular recognition between chiral (handed) molecules. Manmade homogeneous catalysts and enzymes offer complementary means for producing enantiopure (single-handed) compounds. As the subtle details that govern chiral discrimination are difficult to predict, improving the performance of such catalysts often relies on trial-and-error procedures. Homogeneous catalysts are optimized by chemical modification of the chiral environment around the metal center. Enzymes can be improved by modification of gene encoding the protein. Incorporation of a biotinylated organometallic catalyst into a host protein (avidin or streptavidin) affords versatile artificial metalloenzymes for the reduction of ketones by transfer hydrogenation. The boric acid.formate mixture was identified as a hydrogen source compatible with these artificial metalloenzymes. A combined chemo-genetic procedure allows us to optimize the activity and selectivity of these hybrid catalysts: up to 94% (R) enantiomeric excess for the reduction of p-methylacetophenone. These artificial metalloenzymes display features reminiscent of both homogeneous catalysts and enzymes.
authors.affiliation: Institute of Chemistry, University of Neuchâtel, Avenue Bellevaux 51, CP 2, CH-2007 Neuchâtel, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Letondor
authors.forename: Nicolas
authors.initials: N
authors.lastname: Humbert
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ward
mesh_terms: D001710:Biotin / Q000737:chemistry*; D001888:Boric Acids / Q000737:chemistry; D002384:Catalysis; D002616:Chemical Engineering / Q000379:methods; D005561:Formates / Q000737:chemistry; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D008024:Ligands; D045726:Metalloproteases / Q000737:chemistry*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D019809:Streptavidin / Q000737:chemistry*
chemical_list: D001888:Boric Acids; D005561:Formates; D007659:Ketones; D008024:Ligands; C030544:formic acid; D001710:Biotin; D019809:Streptavidin; D045726:Metalloproteases; C032688:boric acid