12 publications

12 publications

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

A Hybrid Ring- Opening Metathesis Polymerization Catalyst Based on an Engineered Variant of the Beta-Barrel Protein FhuA

Okuda, J.; Schwaneberg, U.

Chem. - Eur. J., 2013, 10.1002/chem.201301515

A β‐barrel protein hybrid catalyst was prepared by covalently anchoring a Grubbs–Hoveyda type olefin metathesis catalyst at a single accessible cysteine amino acid in the barrel interior of a variant of β‐barrel transmembrane protein ferric hydroxamate uptake protein component A (FhuA). Activity of this hybrid catalyst type was demonstrated by ring‐opening metathesis polymerization of a 7‐oxanorbornene derivative in aqueous solution.


Metal: Ru
Ligand type: Carbene
Host protein: FhuA ΔCVFtev
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 955
ee: ---
PDB: ---
Notes: ROMP

An Artificial Metalloenzyme for Olefin Metathesis

Hilvert, D.; Ward, T. R.

Chem. Commun., 2011, 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

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: ---

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

Ward, T. R.

Chem. Commun., 2011, 10.1039/c1cc15004a


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

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.

Chimeric Streptavidins as Host Proteins for Artificial Metalloenzymes

Ward, T. R.; Woolfson, D. N.

ACS Catal., 2018, 10.1021/acscatal.7b03773


Metal: Ir
Ligand type: Cp*; Diamine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 970
ee: 13
PDB: ---
Notes: ---

Metal: Ir
Ligand type: Cp*; Diamine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 158
ee: 82
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Carbene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Olefin metathesis
Max TON: 105
ee: ---
PDB: ---
Notes: RCM, biotinylated Hoveyda-Grubbs second generation catalyst

Metal: ---
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Anion-π catalysis
Max TON: 6
ee: 41
PDB: ---
Notes: No metal

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

Chem. Commun., 2012, 10.1039/c2cc16898g


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

Directed Evolution of Artificial Metalloenzymes for In Vivo Metathesis

Panke, S.; Ward, T. R.

Nature, 2016, 10.1038/nature19114


Metal: Ru
Ligand type: Carbene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Olefin metathesis
Max TON: 610
ee: ---
PDB: ---
Notes: Reaction in the periplasm

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

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: ---

Ring-Closing and Cross-Metathesis with Artificial Metalloenzymes Created by Covalent Active Site- Directed Hybridization of a Lipase

Klein Gebbink, R. J. M.

Chem. - Eur. J., 2015, 10.1002/chem.201502381


Metal: Ru
Ligand type: Carbene
Host protein: Cutinase
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 17
ee: ---
PDB: ---
Notes: RCM

Metal: Ru
Ligand type: Carbene
Host protein: Cutinase
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 20
ee: ---
PDB: ---
Notes: Cross metathesis