46 publications

46 publications

A Designed Metalloenzyme Achieving the Catalytic Rate of a Native Enzyme

Lu, Y.; Wang, J.

J. Am. Chem. Soc., 2015, 10.1021/jacs.5b07119

Terminal oxidases catalyze four-electron reduction of oxygen to water, and the energy harvested is utilized to drive the synthesis of adenosine triphosphate. While much effort has been made to design a catalyst mimicking the function of terminal oxidases, most biomimetic catalysts have much lower activity than native oxidases. Herein we report a designed oxidase in myoglobin with an O2 reduction rate (52 s–1) comparable to that of a native cytochrome (cyt) cbb3 oxidase (50 s–1) under identical conditions. We achieved this goal by engineering more favorable electrostatic interactions between a functional oxidase model designed in sperm whale myoglobin and its native redox partner, cyt b5, resulting in a 400-fold electron transfer (ET) rate enhancement. Achieving high activity equivalent to that of native enzymes in a designed metalloenzyme offers deeper insight into the roles of tunable processes such as ET in oxidase activity and enzymatic function and may extend into applications such as more efficient oxygen reduction reaction catalysts for biofuel cells.


Metal: Cu
Ligand type: Amino acid
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Genetic
Reaction: O2 reduction
Max TON: ---
ee: ---
PDB: ---
Notes: O2 reduction rates of 52 s-1 were achieved in combination with the native redox partner cyt b5.

A Highly Active Biohybrid Catalyst for Olefin Metathesis in Water: Impact of a Hydrophobic Cavity in a β-Barrel Protein

Okuda, J.

ACS Catal., 2015, 10.1021/acscatal.5b01792

A series of Grubbs–Hoveyda type catalyst precursors for olefin metathesis containing a maleimide moiety in the backbone of the NHC ligand was covalently incorporated in the cavity of the β-barrel protein nitrobindin. By using two protein mutants with different cavity sizes and choosing the suitable spacer length, an artificial metalloenzyme for olefin metathesis reactions in water in the absence of any organic cosolvents was obtained. High efficiencies reaching TON > 9000 in the ROMP of a water-soluble 7-oxanorbornene derivative and TON > 100 in ring-closing metathesis (RCM) of 4,4-bis(hydroxymethyl)-1,6-heptadiene in water under relatively mild conditions (pH 6, T = 25–40 °C) were observed.


Metal: Ru
Ligand type: Carbene
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 9900
ee: ---
PDB: ---
Notes: ROMP (cis/trans: 48/52)

Metal: Ru
Ligand type: Carbene
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 100
ee: ---
PDB: ---
Notes: RCM

Albumin as a Promiscuous Biocatalyst in Organic Synthesis

Review

Gaggero, N.

RSC Adv., 2015, 10.1039/C4RA11206G

Albumin emerged as a biocatalyst in 1980 and the continuing interest in this protein is proved by numerous papers. The use of albumin was initially confined to the field of asymmetric oxidations and reductions, but more recently it has found a broader application to chemical reactions such as additions, condensations and eliminations. This review reports the main applications of albumin in organic synthesis that have appeared in the literature in the past decade.


Notes: ---

An Artificial Enzyme Made by Covalent Grafting of an FeII Complex into β-Lactoglobulin: Molecular Chemistry, Oxidation Catalysis, and Reaction-Intermediate Monitoring in a Protein

Banse, F.; Mahy, J.-P.

Chem. - Eur. J., 2015, 10.1002/chem.201501755

An artificial metalloenzyme based on the covalent grafting of a nonheme FeII polyazadentate complex into bovine β‐lactoglobulin has been prepared and characterized by using various spectroscopic techniques. Attachment of the FeII catalyst to the protein scaffold is shown to occur specifically at Cys121. In addition, spectrophotometric titration with cyanide ions based on the spin‐state conversion of the initial high spin (S=2) FeII complex into a low spin (S=0) one allows qualitative and quantitative characterization of the metal center’s first coordination sphere. This biohybrid catalyst activates hydrogen peroxide to oxidize thioanisole into phenylmethylsulfoxide as the sole product with an enantiomeric excess of up to 20 %. Investigation of the reaction between the biohybrid system and H2O2 reveals the generation of a high spin (S=5/2) FeIII(η2‐O2) intermediate, which is proposed to be responsible for the catalytic sulfoxidation of the substrate.


Metal: Fe
Ligand type: Poly-pyridine
Host protein: ß-lactoglobulin
Anchoring strategy: Covalent
Optimization: ---
Reaction: Sulfoxidation
Max TON: 5.6
ee: 20
PDB: ---
Notes: ---

An Enantioselective Artificial Suzukiase Based on the Biotin–Streptavidin Technology

Ward, T. R.

Chem. Sci., 2015, 10.1039/c5sc03116h


Metal: Pd
Ligand type: Allyl; Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 88
ee: 80
PDB: ---
Notes: ---

Metal: Pd
Ligand type: Allyl; Carbene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 5
ee: ---
PDB: ---
Notes: ---

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

Utschig, L. M.

Chem. Commun., 2015, 10.1039/c5cc03006d


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

Artificial Diiron Enzymes with a De Novo Designed Four-Helix Bundle Structure

Review

DeGrado, W. F.; Lombardi, A.

Eur. J. Inorg. Chem., 2015, 10.1002/ejic.201500470


Notes: ---

Artificial Hydrogenase: Biomimetic Approaches Controlling Active Molecular Catalysts

Review

Onoda, A.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.041


Notes: ---

Artificial Hydrogenases: Biohybrid and Supramolecular Systems for Catalytic Hydrogen Production or Uptake

Review

Fontecave, M.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.018


Notes: ---

Artificial Metalloenzymes Derived from Three-Helix Bundles

Review

Pecoraro, V. L.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.034


Notes: ---

Artificial Metalloenzymes for Asymmetric Catalysis by Creation of Novel Active Sites in Protein and DNA Scaffolds

Review

Roelfes, G.

Isr. J. Chem., 2015, 10.1002/ijch.201400094


Notes: ---

Artificial Metalloenzymes for the Diastereoselective Reduction of NAD+ to NAD2H

Ward, T. R.

Org. Biomol. Chem., 2015, 10.1039/c4ob02071e


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

Artificial Metalloenzymes in Asymmetric Catalysis: Key Developments and Future Directions

Review

Bäckvall, J. E.; Diéguez, M.; Pàmies, O.

Adv. Synth. Catal., 2015, 10.1002/adsc.201500290


Notes: ---

Carbonic Anhydrase II as Host Protein for the Creation of a Biocompatible Artificial Metathesase

Ward, T. R.

Org. Biomol. Chem., 2015, 10.1039/c5ob00428d


Metal: Ru
Ligand type: Carbene
Anchoring strategy: Dative
Optimization: Chemical & genetic
Reaction: Olefin metathesis
Max TON: 28
ee: ---
PDB: ---
Notes: Ring closing metathesis. 28 turnovers obtained under physiological conditions within 4 hours.

Defining the Role of Tyrosine and Rational Tuning of Oxidase Activity by Genetic Incorporation of Unnatural Tyrosine Analogs

Lu, Y.; Wang, J.

J. Am. Chem. Soc., 2015, 10.1021/ja5109936


Metal: Cu
Ligand type: Porphyrin
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: 1200
ee: ---
PDB: 4FWX
Notes: Sperm whale myoglobin

De Novo Protein Design as a Methodology for Synthetic Bioinorganic Chemistry

Review

Pecoraro, V. L.

Acc. Chem. Res., 2015, 10.1021/acs.accounts.5b00175


Notes: ---

Directed Evolution of Artificial Metalloenzymes

Review

Reetz, M. T.

Isr. J. Chem., 2015, 10.1002/ijch.201400087


Notes: ---

Direct Hydrogenation of Carbon Dioxide by an Artificial Reductase Obtained by Substituting Rhodium for Zinc in the Carbonic Anhydrase Catalytic Center. A Mechanistic Study

Marino, T.

ACS Catal., 2015, 10.1021/acscatal.5b00185


Metal: Rh
Ligand type: Amino acid
Anchoring strategy: Metal substitution
Optimization: ---
Reaction: Hydrogenation
Max TON: ---
ee: ---
PDB: ---
Notes: Computational study of the reaction mechanism of the formation of HCOOH from CO2

Engineering a Dirhodium Artificial Metalloenzyme for Selective Olefin Cyclopropanation

Lewis, J. C.

Nat. Commun., 2015, 10.1038/ncomms8789


Metal: Rh
Ligand type: Poly-carboxylic acid
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: 74
ee: 92
PDB: ---
Notes: ---

Enzyme Repurposing of a Hydrolase as an Emergent Peroxidase Upon Metal Binding

Fujieda, N.; Ward, T. R.

Chem. Sci., 2015, 10.1039/c5sc01065a


Metal: Cu
Ligand type: Amino acid
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 35
ee: ---
PDB: ---
Notes: ---

From Enzyme Maturation to Synthetic Chemistry: The Case of Hydrogenases

Review

Fontecave, M.

Acc. Chem. Res., 2015, 10.1021/acs.accounts.5b00157


Notes: ---

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

Review

Mahy, J.-P.

Chem. Commun., 2015, 10.1039/c4cc08169b


Notes: ---

Generation of New Artificial Metalloproteins by Cofactor Modification of Native Hemoproteins

Review

Isr. J. Chem., 2015, 10.1002/ijch.201400123


Notes: ---

Hybrid [FeFe]-Hydrogenases with Modified Active Sites Show Remarkable Residual Enzymatic Activity

Lubitz, W.; Reijerse, E.

Biochemistry, 2015, 10.1021/bi501391d


Metal: Fe
Ligand type: CN; CO; Dithiolate
Anchoring strategy: Dative
Optimization: Chemical
Max TON: ---
ee: ---
PDB: ---
Notes: H2 evolution: TOF = 450 s-1. H2 oxidation: TOF = 150 s-1.

Hybrid Ruthenium ROMP Catalysts Based on an Engineered Variant of β-Barrel Protein FhuA ΔCVFtev: Effect of Spacer Length

Okuda, J.

Chem. - Asian J., 2015, 10.1002/asia.201403005


Metal: Ru
Ligand type: Carbene
Host protein: FhuA ΔCVFtev
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 555
ee: ---
PDB: ---
Notes: ROMP; cis/trans = 58/42

Improving the Catalytic Performance of an Artificial Metalloenzyme by Computational Design

Baker, D.; Ward, T. R.

J. Am. Chem. Soc., 2015, 10.1021/jacs.5b06622


Metal: Ir
Ligand type: Cp*; Pyridine sulfonamide
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 100
ee: 96
PDB: ---
Notes: ---

Latest Developments in Metalloenzyme Design and Repurposing

Review

Ward, T. R.

Eur. J. Inorg. Chem., 2015, 10.1002/ejic.201500408


Notes: ---

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

Klein Gebbink, R. J. M.

Chem. Commun., 2015, 10.1039/c4cc09700a


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: ---

Metal-Binding Promiscuity in Artificial Metalloenzyme Design

Review

Pordea, A.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.035


Notes: ---

Metallopeptide Catalysts and Artificial Metalloenzymes Containing Unnatural Amino Acids

Review

Lewis, J. C.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.016


Notes: ---