Aqueous Oxidation of Alcohols Catalyzed by Artificial Metalloenzymes Based on the Biotin–Avidin Technology
J. Organomet. Chem. 2005, 690, 4488-4491, 10.1016/j.jorganchem.2005.02.001
Based on the incorporation of biotinylated organometallic catalyst precursors within (strept)avidin, we have developed artificial metalloenzymes for the oxidation of secondary alcohols using tert-butylhydroperoxide as oxidizing agent. In the presence of avidin as host protein, the biotinylated aminosulfonamide ruthenium piano stool complex 1 (0.4 mol%) catalyzes the oxidation of sec-phenethyl alcohol at room temperature within 90 h in over 90% yield. Gel electrophoretic analysis of the reaction mixture suggests that the host protein is not oxidatively degraded during catalysis.
Max TON: 200ee: ---PDB: ---Notes: ---
Host protein: Avidin (Av)Max TON: 230ee: ---PDB: ---Notes: ---
Ligand type: Bipyridine; C6Me6Max TON: 173ee: ---PDB: ---Notes: ---
Max TON: 7.5ee: ---PDB: ---Notes: ---
Ligand type: Bipyridine; Cp*Max TON: 30ee: ---PDB: ---Notes: ---
Artificial Metalloenzymes Based on Biotin-Avidin Technology for the Enantioselective Reduction of Ketones by Transfer Hydrogenation
Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 4683-4687, 10.1073/pnas.0409684102
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.
Max TON: 92ee: 94PDB: ---Notes: ---
Max TON: 30ee: 63PDB: ---Notes: ---
Artificial Transfer Hydrogenases Based on the Biotin-(Strept)avidin Technology: Fine Tuning the Selectivity by Saturation Mutagenesis of the Host Protein
J. Am. Chem. Soc. 2006, 128, 8320-8328, 10.1021/ja061580o
Incorporation of biotinylated racemic three-legged d6-piano stool complexes in streptavidin yields enantioselective transfer hydrogenation artificial metalloenzymes for the reduction of ketones. Having identified the most promising organometallic catalyst precursors in the presence of wild-type streptavidin, fine-tuning of the selectivity is achieved by saturation mutagenesis at position S112. This choice for the genetic optimization site is suggested by docking studies which reveal that this position lies closest to the biotinylated metal upon incorporation into streptavidin. For aromatic ketones, the reaction proceeds smoothly to afford the corresponding enantioenriched alcohols in up to 97% ee (R) or 70% (S). On the basis of these results, we suggest that the enantioselection is mostly dictated by CH/π interactions between the substrate and the η6-bound arene. However, these enantiodiscriminating interactions can be outweighed in the presence of cationic residues at position S112 to afford the opposite enantiomers of the product.
Max TON: 96ee: 80PDB: ---Notes: ---
Max TON: 73ee: 60PDB: ---Notes: ---
Max TON: 95ee: 70PDB: ---Notes: ---
Max TON: 79ee: 97PDB: ---Notes: ---
Artificial Transfer Hydrogenases for the Enantioselective Reduction of Cyclic Imines
Angew. Chem. Int. Ed. 2011, 50, 3026-3029, 10.1002/anie.201007820
Man‐made activity: Introduction of a biotinylated iridium piano stool complex within streptavidin affords an artificial imine reductase (see scheme). Saturation mutagenesis allowed optimization of the activity and the enantioselectivity of this metalloenzyme, and its X‐ray structure suggests that a nearby lysine residue acts as a proton source during the transfer hydrogenation.
Max TON: 4000ee: 96Notes: ---
Max TON: 94ee: 52Notes: ---
Max TON: 97ee: 22Notes: ---
Max TON: 76ee: 12Notes: ---
Improving the Enantioselectivity of Artificial Transfer Hydrogenases Based on the Biotin–Streptavidin Technology by Combinations of Point Mutations
Inorg. Chim. Acta 2010, 363, 601-604, 10.1016/j.ica.2009.02.001
Artificial metalloenzymes based on the incorporation of biotinylated ruthenium piano–stool complexes within streptavidin can be readily optimized by chemical or genetic means. We performed genetic modifications of such artificial metalloenzymes for the transfer hydrogenation of aromatic ketones, by combining targeted point mutations of the host protein. Upon using the P64G-L124V double mutant of streptavidin in combination with the [η6-(p-cymene)Ru(Biot-p-L)Cl] complex, the enantioselectivity can be increased up to 98% ee (R) for the reduction of p-methylacetophenone, which is the highest selectivity obtained up to date with an artificial transfer hydrogenase.
Max TON: 98ee: 98PDB: ---Notes: ---
Max TON: 24ee: 84Notes: ---
Metal-Conjugated Affinity Labels: A New Concept to Create Enantioselective Artificial Metalloenzymes
ChemistryOpen 2013, 2, 50-54, 10.1002/open.201200044
How to train a protein: Metal‐conjugated affinity labels were used to selectively position catalytically active metal centers in the binding pocket of proteases. The resulting artificial metalloenzymes achieve up to 82 % e.r. in the hydrogenation of ketones. The modular setup enables a rapid generation of artificial metalloenzyme libraries, which can be adapted to a broad range of catalytic conditions.
Host protein: Papain (PAP)Reaction: HydrogenationMax TON: 89ee: 64PDB: ---Notes: ---
Porous Protein Crystals as Catalytic Vessels for Organometallic Complexes
Chem. - Asian J. 2014, 9, 1373-1378, 10.1002/asia.201301347
Porous protein crystals, which are protein assemblies in the solid state, have been engineered to form catalytic vessels by the incorporation of organometallic complexes. Ruthenium complexes in cross‐linked porous hen egg white lysozyme (HEWL) crystals catalyzed the enantioselective hydrogen‐transfer reduction of acetophenone derivatives. The crystals accelerated the catalytic reaction and gave different enantiomers based on the crystal form (tetragonal or orthorhombic). This method represents a new approach for the construction of bioinorganic catalysts from protein crystals.
Ligand type: BenzeneHost protein: Lysozyme (crystal)Anchoring strategy: DativeOptimization: ---Max TON: ---ee: ---PDB: 3W6ANotes: Tetragonal HEWL crystals
Ligand type: BenzeneHost protein: Lysozyme (crystal)Anchoring strategy: DativeOptimization: ---Max TON: ---ee: ---PDB: 4J7VNotes: Orthorhombic HEWL crystals
X-Ray Structure and Designed Evolution of an Artificial Transfer Hydrogenase
Angew. Chem. Int. Ed. 2008, 47, 1400-1404, 10.1002/anie.200704865
A structure is worth a thousand words: Guided by the X‐ray structure of an S‐selective artificial transfer hydrogenase, designed evolution was used to optimize the selectivity of hybrid catalysts. Fine‐tuning of the second coordination sphere of the ruthenium center (see picture, orange sphere) by introduction of two point mutations allowed the identification of selective artificial transfer hydrogenases for the reduction of dialkyl ketones.
Max TON: 100ee: 92Notes: ---
Max TON: 97ee: 96Notes: ---
(η6-Arene) Ruthenium(II) Complexes and Metallo-Papain Hybrid as Lewis Acid Catalysts of Diels–Alder Reaction in Water
Dalton Trans. 2010, 39, 5605, 10.1039/c001630f
Covalent embedding of a (η6-arene) ruthenium(II) complex into the protein papain gives rise to a metalloenzyme displaying a catalytic efficiency for a Lewis acid-mediated catalysed Diels–Alder reaction enhanced by two orders of magnitude in water.
Ligand type: Benzene; PhenanthrolineHost protein: Papain (PAP)Reaction: Diels-Alder reactionMax TON: 440ee: ---PDB: ---Notes: TOF = 220 h-1