22 publications

22 publications

A Hydrogenase Model System Based on the Sequence of Cytochrome c: Photochemical Hydrogen Evolution in Aqueous Media

Hayashi, T

Chem. Commun. 2011, 47, 8229, 10.1039/c1cc11157d

The diiron carbonyl cluster is held by a native CXXC motif, which includes Cys14 and Cys17, in the cytochrome c sequence. It is found that the diiron carbonyl complex works well as a catalyst for H2 evolution. It has a TON of ∼80 over 2 h at pH 4.7 in the presence of a Ru-photosensitizer and ascorbate as a sacrificial reagent in aqueous media.


Metal: Fe
Ligand type: Carbonyl
Host protein: Cytochrome c
Anchoring strategy: Dative
Optimization: ---
Reaction: H2 evolution
Max TON: 82
ee: ---
PDB: ---
Notes: Horse heart cytochrome C

An Artificial Metalloenzyme for Olefin Metathesis

Hilvert, D.; Ward, T.R.

Chem. Commun. 2011, 47, 12068, 10.1039/c1cc15005g

A Grubbs–Hoveyda type olefin metathesis catalyst, equipped with an electrophilic bromoacetamide group, was used to modify a cysteine-containing variant of a small heat shock protein from Methanocaldococcus jannaschii. The resulting artificial metalloenzyme was found to be active under acidic conditions in a benchmark ring closing metathesis reaction.


Metal: Ru
Ligand type: Carbene
Anchoring strategy: Covalent
Optimization: ---
Reaction: Olefin metathesis
Max TON: 25
ee: ---
PDB: ---
Notes: RCM

Aqueous Light Driven Hydrogen Production by a Ru–Ferredoxin–Co Biohybrid

Utschig, L.M.

Chem. Commun. 2015, 51, 10628-10631, 10.1039/c5cc03006d

Long-lived charge separation facilitates photocatalytic H2 production in a mini reaction center/catalyst complex.


Metal: Co
Ligand type: Oxime
Host protein: Ferredoxin (Fd)
Anchoring strategy: Dative
Optimization: ---
Reaction: H2 evolution
Max TON: 210
ee: ---
PDB: ---
Notes: Recalculated TON

A Rhodium Complex-Linked β-Barrel Protein as a Hybrid Biocatalyst for Phenylacetylene Polymerization

Hayashi, T

Chem. Commun. 2012, 48, 9756, 10.1039/C2CC35165J

Our group recently prepared a hybrid catalyst containing a rhodium complex, Rh(Cp)(cod), with a maleimide moiety at the peripheral position of the Cp ligand. This compound was then inserted into a β-barrel protein scaffold of a mutant of aponitrobindin (Q96C) via a covalent linkage. The hybrid protein is found to act as a polymerization catalyst and preferentially yields trans-poly(phenylacetylene) (PPA), although the rhodium complex without the protein scaffold normally produces cis PPA.


Metal: Rh
Ligand type: COD; Cp*
Host protein: Nitrobindin (Nb)
Anchoring strategy: Cystein-maleimide
Optimization: ---
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Artificial Metalloenzymes for Olefin Metathesis Based on the Biotin-(Strept)Avidin Technology

Ward, T.R.

Chem. Commun. 2011, 47, 12065, 10.1039/c1cc15004a

Incorporation of a biotinylated Hoveyda-Grubbs catalyst within (strept)avidin affords artificial metalloenzymes for the ring-closing metathesis of N-tosyl diallylamine in aqueous solution. Optimization of the performance can be achieved either by chemical or genetic means.


Metal: Ru
Ligand type: Carbene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 14
ee: ---
PDB: ---
Notes: RCM

Metal: Ru
Ligand type: Carbene
Host protein: Avidin (Av)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 19
ee: ---
PDB: ---
Notes: RCM

Chemical Optimization of Artificial Metalloenzymes Based on the Biotin-Avidin Technology: (S)-Selective and Solvent-Tolerant Hydrogenation Catalysts via the Introduction of Chiral Amino Acid Spacers

Ward, T.R.

Chem. Commun. 2005, 4815, 10.1039/b509015f

Incorporation of biotinylated-[rhodium(diphosphine)]+ complexes, with enantiopure amino acid spacers, in streptavidin affords solvent-tolerant and selective artificial metalloenzymes: up to 91% ee (S) in the hydrogenation of N-protected dehydroamino acids.


Metal: Rh
Ligand type: Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Chemogenetic Protein Engineering: An Efficient Tool for the Optimization of Artificial Metalloenzymes

Review

Ward, T.R.

Chem. Commun. 2008, 4239, 10.1039/b806652c

Artificial metalloenzymes, based on the incorporation of a catalytically active organometallic moiety within a host protein, lie at the interface between organometallic and enzymatic catalysis. In terms of activity, reaction repertoire, substrate range and operating conditions, they take advantage of the versatility of the organometallic chemistry. In contrast, the enantioselectivity is determined by the biomolecular scaffold, which provides a well defined second coordination sphere to the organometallic moiety, reminiscent of enzymes. The attractive feature of such systems is their optimization potential, which combines chemical and genetic methods (i.e. chemogenetic) to screen diversity space. This feature article describes the implementation of such an optimization protocol for artificial transfer hydrogenases, for which we have the most detailed understanding.


Notes: ---

Creation of an Artificial Metalloprotein with a Hoveyda–Grubbs Catalyst Moiety through the Intrinsic Inhibition Mechanism of α-Chymotrypsin

Chem. Commun. 2012, 48, 1662, 10.1039/c2cc16898g

An L-phenylalanyl chloromethylketone-based inhibitor equipped with a Hoveyda–Grubbs catalyst moiety was regioselectively incorporated into the cleft of α-chymotrypsin through the intrinsic inhibition mechanism of the protein to construct an artificial organometallic protein.


Metal: Ru
Ligand type: Carbene
Host protein: α-chymotrypsin
Anchoring strategy: Covalent
Optimization: ---
Reaction: Olefin metathesis
Max TON: 20
ee: ---
PDB: ---
Notes: RCM

Definite Coordination Arrangement of Organometallic Palladium Complexes Accumulated on the Designed Interior Surface of Apo-Ferritin

Ueno, T.

Chem. Commun. 2011, 47, 170-172, 10.1039/C0CC02221G

Apo-ferritin (apo-Fr) mutants are used as scaffolds to accommodate palladium (allyl) complexes. Various coordination arrangements of the Pd complexes are achieved by adjusting the positions of cysteine and histidine residues on the interior surface of the apo-Fr cage.


Metal: Pd
Ligand type: Allyl
Host protein: Ferritin
Anchoring strategy: Dative
Optimization: Genetic
Reaction: Suzuki coupling
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Directed Evolution of Hybrid Enzymes: Evolving Enantioselectivity of an Achiral Rh-Complex Anchored to a Protein

Reetz, M.T.

Chem. Commun. 2006, 4318, 10.1039/b610461d

The concept of utilizing the methods of directed evolution for tuning the enantioselectivity of synthetic achiral metal–ligand centers anchored to proteins has been implemented experimentally for the first time.


Metal: Rh
Ligand type: COD; Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Hydrogenation
Max TON: 4500
ee: 65
PDB: ---
Notes: ---

Dual Modification of a Triple-Stranded β-Helix Nanotube with Ru and Re Metal Complexes to Promote Photocatalytic Reduction of CO2

Ueno, T.

Chem. Commun. 2011, 47, 2074, 10.1039/C0CC03015E

We have constructed a robust β-helical nanotube from the component proteins of bacteriophage T4 and modified this nanotube with RuII(bpy)3 and ReI(bpy)(CO)3Cl complexes. The photocatalytic system arranged on the tube catalyzes the reduction of CO2 with higher reactivity than that of the mixture of the monomeric forms.


Metal: Re
Ligand type: Bipyridine; CO
Host protein: [(gp5βf)3]2
Anchoring strategy: Cystein-maleimide
Optimization: ---
Reaction: CO2 reduction
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Bipyridine
Host protein: [(gp5βf)3]2
Anchoring strategy: Lysine-succinimide
Optimization: Genetic
Reaction: CO2 reduction
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Enantioselective Sulfoxidation Mediated by Vanadium-Incorporated Phytase: A Hydrolase Acting as a Peroxidase

Sheldon, R.A.

Chem. Commun. 1998, 1891-1892, 10.1039/a804702b

Phytase (E.C. 3.1.3.8), which in vivo mediates the hydrolysis of phosphate esters, catalyses the enantioselective oxidation of thioanisole with H2O2, both in the presence and absence of vanadate ion, affording the S-sulfoxide in up to 66% ee at 100% conversion.


Metal: V
Ligand type: Undefined
Host protein: Phytase
Anchoring strategy: Undefined
Optimization: ---
Reaction: Sulfoxidation
Max TON: ~194
ee: 66
PDB: ---
Notes: ---

Metal: V
Ligand type: Oxide
Host protein: Phytase
Anchoring strategy: Undefined
Optimization: ---
Reaction: Sulfoxidation
Max TON: 550
ee: 66
PDB: ---
Notes: ---

Enantioselective Transfer Hydrogenation of Ketone Catalysed by Artificial Metalloenzymes Derived from Bovine β-Lactoglobulin

Salmain, M.

Chem. Commun. 2012, 48, 11984, 10.1039/c2cc36980j

Artificial metalloproteins resulting from the embedding of half-sandwich Ru(II)/Rh(III) fatty acid derivatives within β-lactoglobulin catalysed the asymmetric transfer hydrogenation of trifluoroacetophenone with modest to good conversions and fair ee's.


Metal: Rh
Ligand type: Cp*; Poly-pyridine
Host protein: ß-lactoglobulin
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: 34
ee: 26
PDB: ---
Notes: ---

From "Hemoabzymes" to "Hemozymes": Towards new Biocatalysts for Selective Oxidations

Review

Mahy, J.-P.

Chem. Commun. 2015, 51, 2476-2494, 10.1039/c4cc08169b

The design of artificial hemoproteins that could catalyze selective oxidations using clean oxidants such as O2 or H2O2 under ecocompatible conditions constitutes a real challenge for a wide range of industrial applications. In vivo, such reactions are performed by heme-thiolate proteins, cytochromes P450, which catalyze the oxidation of substrates by dioxygen in the presence of electrons delivered from NADPH by cytochrome P450 reductase. Several strategies were used to design new artificial hemoproteins that mimic these enzymes. The first one involved the non-covalent association of synthetic hemes with monoclonal antibodies raised against these cofactors. This led to the first generation of artificial hemoproteins or “hemoabzymes” that displayed a peroxidase activity, and in some cases catalyzed the regioselective nitration of phenols by H2O2/NO2 and the stereoselective oxidation of sulfides by H2O2. The second one involved the non-covalent association of easily affordable non-relevant proteins with metalloporphyrin derivatives, using either the “Trojan Horse strategy” or the “host–guest” strategy. This led to a second generation of artificial hemoproteins or “hemozymes”, some of which were found able to catalyze the stereoselective oxidation of organic compounds such as sulfides and alkenes by H2O2 and KHSO5.


Notes: ---

Immobilization of an Artificial Imine Reductase Within Silica Nanoparticles Improves its Performance

Shahgaldian, P.; Ward, T.R.

Chem. Commun. 2016, 52, 9462-9465, 10.1039/c6cc04604e

Silica nanoparticles equipped with an artificial imine reductase display remarkable activity towards cyclic imine- and NAD+ reduction. The method, based on immobilization and protection of streptavidin on silica nanoparticles, shields the biotinylated metal cofactor against deactivation yielding over 46 000 turnovers in pure samples and 4000 turnovers in crude cellular extracts.


Metal: Ir
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 4554
ee: 89
PDB: ---
Notes: Reaction in nanoparticles

Immobilization of Two Organometallic Complexes into a Single Cage to Construct Protein-Based Microcompartment

Ueno, T.

Chem. Commun. 2016, 52, 5463-5466, 10.1039/C6CC00679E

Natural protein-based microcompartments containing multiple enzymes promote cascade reactions within cells. We use the apo-ferritin protein cage to mimic such biocompartments by immobilizing two organometallic Ir and Pd complexes into the single protein cage. Precise locations of the metals and their accumulation mechanism were studied by X-ray crystallography.


Metal: Ir
Ligand type: Amino acid; Cp*
Host protein: Apo-ferritin
Anchoring strategy: Dative
Optimization: Chemical
Reaction: Hydrogenation
Max TON: ~2
ee: 15
PDB: 5E2D
Notes: Tandem reaction (Hydrogenation and Suzuki-Miyaura coupling) to form biphenylethanol from 4-iodoacetophenone and phenylboronic acid. TON and ee are given for the tandem reaction product.

Metal: Pd
Ligand type: Allyl; Amino acid
Host protein: Apo-ferritin
Anchoring strategy: Dative
Optimization: Chemical
Max TON: ~1
ee: 15
PDB: 5E2D
Notes: Tandem reaction (Hydrogenation and Suzuki-Miyaura coupling) to form biphenylethanol from 4-iodoacetophenone and phenylboronic acid.

Lipase Active Site Covalent Anchoring of Rh(NHC) Catalysts: Towards Chemoselective Artificial Metalloenzymes

Klein Gebbink, R.J.M.

Chem. Commun. 2015, 51, 6792-6795, 10.1039/c4cc09700a

A Rh(NHC) phosphonate complex reacts with the lipases cutinase and Candida antarctica lipase B resulting in the first (soluble) artificial metalloenzymes formed by covalent active site-directed hybridization. When compared to unsupported complexes, these new robust hybrids show enhanced chemoselectivity in the (competitive) hydrogenation of olefins over ketones.


Metal: Rh
Ligand type: Carbene
Host protein: Cutinase
Anchoring strategy: Covalent
Optimization: ---
Reaction: Hydrogenation
Max TON: 20
ee: rac.
PDB: 1CEX
Notes: ---

Metal: Rh
Ligand type: Carbene
Anchoring strategy: Covalent
Optimization: ---
Reaction: Hydrogenation
Max TON: 20
ee: rac.
PDB: 4K6G
Notes: ---

Merging Homogeneous Catalysis with Biocatalysis; Papain as Hydrogenation Catalyst

de Vries, J.

Chem. Commun. 2005, 5656, 10.1039/B512138H

Papain, modified at Cys-25 with a monodentate phosphite ligand and complexed with Rh(COD)2BF4, is an active catalyst in the hydrogenation of methyl 2-acetamidoacrylate.


Metal: Rh
Ligand type: Phosphine
Host protein: Papain (PAP)
Anchoring strategy: Covalent
Optimization: ---
Reaction: Hydrogenation
Max TON: 400
ee: <10
PDB: ---
Notes: ---

Merging the Best of Two Worlds: Artificial Metalloenzymes for Enantioselective Catalysis

Review

Ward, T.R.

Chem. Commun. 2011, 47, 8470, 10.1039/c1cc11592h

Artificial metalloenzymes result from combining a catalytically active organometallic moiety with a macromolecular host. The resulting hybrid catalysts combine attractive features of both homogeneous and enzymatic systems. Herein we summarize the recent progress in this emerging field and outline the challenges ahead.


Notes: ---

Protein Scaffold of a Designed Metalloenzyme Enhances the Chemoselectivity in Sulfoxidation of Thioanisole

Lu, Y.

Chem. Commun. 2008, 1665, 10.1039/b718915j

We demonstrate that incorporation of MnSalen into a protein scaffold enhances the chemoselectivity in sulfoxidation of thioanisole and find that both the polarity and hydrogen bonding of the protein scaffold play an important role in tuning the chemoselectivity.


Metal: Mn
Ligand type: Salen
Host protein: Myoglobin (Mb)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Sulfoxidation
Max TON: 5.2
ee: 60
PDB: ---
Notes: Sperm whale myoglobin

Protein Secondary-Shell Interactions Enhance the Photoinduced Hydrogen Production of Cobalt Protoporphyrin IX

Ghirlanda, G.

Chem. Commun. 2014, 50, 15852-15855, 10.1039/c4cc06700b

Hydrogen is an attractive fuel with potential for production scalability, provided that inexpensive, efficient molecular catalysts utilizing base metals can be developed for hydrogen production. Here we show for the first time that cobalt myoglobin (CoMyo) catalyzes hydrogen production in mild aerobic conditions with turnover number of 520 over 8 hours. Compared to free Co-protoporphyrin IX, incorporation into the myoglobin scaffold results in a 4-fold increase in photoinduced hydrogen production activity. Engineered variants in which specific histidine resides in proximity of the active site were mutated to alanine result in modulation of the catalytic activity, with the H64A/H97A mutant displaying activity 2.5-fold higher than wild type. Our results demonstrate that protein scaffolds can augment and modulate the intrinsic catalytic activity of molecular hydrogen production catalysts.


Metal: Co
Ligand type: Porphyrin
Host protein: Myoglobin (Mb)
Anchoring strategy: Metal substitution
Optimization: Genetic
Reaction: H2 evolution
Max TON: 518
ee: ---
PDB: ---
Notes: ---

Synthesis of a Heterogeneous Artificial Metallolipase with Chimeric Catalytic Activity

Filice, M.

Chem. Commun. 2015, 51, 9324-9327, 10.1039/C5CC02450A

A solid-phase strategy using lipase as a biomolecular scaffold to produce a large amount of Cu2+-metalloenzyme is proposed here. The application of this protocol on different 3D cavities of the enzyme allows creating a heterogeneous artificial metallolipase showing chimeric catalytic activity. The artificial catalyst was assessed in Diels–Alder cycloaddition reactions and cascade reactions showing excellent catalytic properties.


Metal: Cu
Ligand type: Phenanthroline
Anchoring strategy: Covalent
Optimization: Genetic
Max TON: 411
ee: 92
PDB: ---
Notes: ArM is immobilized on Sepabeads. Endo/exo = 93.5%

Metal: Cu
Ligand type: Phenanthroline
Anchoring strategy: Covalent
Optimization: Genetic
Reaction: Reduction
Max TON: ---
ee: ---
PDB: ---
Notes: Cascade reaction: Ester hydrolysis (natural function of the host protein) followed by reduction (function of the designed ArM).