Artificial metalloenzymes are hybrids of homogeneous and enzymatic catalysis. They combine the high activity and selectivity of enzymatic catalysis with the versatility of organometallic catalysts. The most common approaches for creating artificial metalloenzymes involve covalent, dative or supramolecular anchoring of the synthetic ligand/transition metal catalysts to the host protein [1]. Here, we introduce a new strategy that involves in-vivo incorporation of the metal-binding unnatural amino acid (2,2?bipyridin-5yl)alanine (Bpy-Ala) into the protein [2].The transcription factor LmrR (Lactococcal multidrug resistance Regulator), which contains a hydrophobic pocket at the dimer interface was chosen as the host protein scaffold [3]. Three positions, Asn 19, Met 89 and Phe 93, located at the different positions of the hydrophobic pocket, were mutated to incorporate the unnatural amino acid Bpy-Ala. Upon binding Cu2+, the resulting artificial metalloenzyme was capable of catalyzing several types of reactions including Friedel-Crafts and water addition reactions with moderate to good values of eeand conversions. A mutagenesis study was carried out to identify essential residues for catalysis in order to further enhance conversion and enantiomeric excess of the reactions. [1] Rosati, F and Roelfes, G., ChemCatChem., 2 (2010) 916-927.[2] Xie, J., Liu, W and Schultz, P.G., Angew. Chem. Int. Ed., 46 (2007) 9239-9242.[3] Madoori, P. K., Agustiandari, H., Driessen, A. J. M and Thunnissen, A. W. H., EMBO Journal, 28 (2009) 156-166.

New design of an artificial metalloenzyme utilizing an unnatural amino acid

248th National Meeting (2014)

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