109 publications

109 publications

8-Amino-5,6,7,8-tetrahydroquinoline in Iridium(III) Biotinylated Cp* Complex as Artificial Imine Reductase

Rimoldi, I.

New J. Chem., 2018, 10.1039/C8NJ04558E

Diamine ligands I–IV coordinated to an iridium metal complex with the biotin moiety anchored to the Cp* ring were investigated. This strategy, in contrast to the traditional biotin–streptavidin technology that uses a biotinylated ligand in the artificial imine reductase, is practical for envisaging how the enantiodiscrimination by different Streptavidin (Sav) mutants could influence the chiral environment of the metal cofactor. Only in the case of (R)-CAMPY IV did the chirality at the metal centre and the second coordination sphere environment, which was dictated by the host protein, operate in a synergistic way, producing better enantioselectivity at a S112M Sav catalyst/catalyst ratio of 1.0 : 2.5. Under these optimized conditions, the artificial imine reductase afforded a good enantiomeric excess (83%) in the asymmetric transfer hydrogenation of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline.


Metal: Ir
Ligand type: Cp*; Diamine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 32
ee: 83
PDB: ---
Notes: ---

Metal: Ir
Ligand type: Cp*; Diamine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 99
ee: 13
PDB: ---
Notes: ---

A Cell-Penetrating Artificial Metalloenzyme Regulates a Gene Switch in a Designer Mammalian Cell

Fussenegger, M.; Matile, S.; Ward, T. R.

Nat. Commun., 2018, 10.1038/s41467-018-04440-0

Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin–streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.


Metal: Ru
Ligand type: Cp; Quinoline
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Deallylation
Max TON: 33
ee: ---
PDB: ---
Notes: ---

Achiral Cyclopentadienone Iron Tricarbonyl Complexes Embedded in Streptavidin: An Access to Artificial Iron Hydrogenases and Application in Asymmetric Hydrogenation

Renaud, J.-L.; Ward, T. R.

Catal. Lett., 2016, 10.1007/s10562-015-1681-6

We report on the synthesis of biotinylated (cyclopentadienone)iron tricarbonyl complexes, the in situ generation of the corresponding streptavidin conjugates and their application in asymmetric hydrogenation of imines and ketones.


Metal: Fe
Ligand type: CO; Cyclopentadienone
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: 20
ee: 34
PDB: ---
Notes: ---

Addressable DNA–Myoglobin Photocatalysis

Niemeyer, C. M.

Chem. - Asian J., 2009, 10.1002/asia.200900082

A hybrid myoglobin, containing a single‐stranded DNA anchor and a redox‐active ruthenium moiety tethered to the heme center can be used as a photocatalyst. The catalyst can be selectively immobilized on a surface‐bound complementary DNA molecule and thus readily recycled from complex reaction mixtures. This principle may be applied to a range of heme‐dependent enzymes allowing the generation of novel light‐triggered photocatalysts. Photoactivatable myoglobin containing a DNA oligonucleotide as a structural anchor was designed by using the reconstitution of artificial heme moieties containing Ru3+ ions. This semisynthetic DNA–enzyme conjugate was successfully used for the oxidation of peroxidase substrates by using visible light instead of H2O2 for the activation. The DNA anchor was utilized for the immobilization of the enzyme on the surface of magnetic microbeads. Enzyme activity measurements not only indicated undisturbed biofunctionality of the tethered DNA but also enabled magnetic separation‐based enrichment and recycling of the photoactivatable biocatalyst.


Metal: Ru
Ligand type: Bipyridine
Host protein: Myoglobin (Mb)
Anchoring strategy: Supramolecular
Optimization: ---
Reaction: Photooxidation
Max TON: ---
ee: ---
PDB: ---
Notes: Horse heart myoglobin

A Dual Anchoring Strategy for the Localization and Activation of Artificial Metalloenzymes Based on the Biotin−Streptavidin Technology

Ward, T. R.

J. Am. Chem. Soc., 2013, 10.1021/ja309974s

Artificial metalloenzymes result from anchoring an active catalyst within a protein environment. Toward this goal, various localization strategies have been pursued: covalent, supramolecular, or dative anchoring. Herein we show that introduction of a suitably positioned histidine residue contributes to firmly anchor, via a dative bond, a biotinylated rhodium piano stool complex within streptavidin. The in silico design of the artificial metalloenzyme was confirmed by X-ray crystallography. The resulting artificial metalloenzyme displays significantly improved catalytic performance, both in terms of activity and selectivity in the transfer hydrogenation of imines. Depending on the position of the histidine residue, both enantiomers of the salsolidine product can be obtained.


Metal: Ir
Ligand type: Amino acid; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 14
ee: 11
PDB: ---
Notes: ---

Metal: Rh
Ligand type: Amino acid; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 100
ee: 79
PDB: ---
Notes: ---

Albumin-Conjugated Corrole Metal Complexes: Extremely Simple Yet Very Efficient Biomimetic Oxidation Systems

Gross, Z.

J. Am. Chem. Soc., 2005, 10.1021/ja045372c

An extremely simple biomimetic oxidation system, consisting of mixing metal complexes of amphiphilic corroles with serum albumins, utilizes hydrogen peroxide for asymmetric sulfoxidation in up to 74% ee. The albumin-conjugated manganese corroles also display catalase-like activity, and mechanistic evidence points toward oxidant-coordinated manganese(III) as the prime reaction intermediate.


Metal: Mn
Ligand type: Corrole
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Sulfoxidation
Max TON: 8
ee: 74
PDB: ---
Notes: ---

Metal: Mn
Ligand type: Corrole
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Sulfoxidation
Max TON: 42
ee: 52
PDB: ---
Notes: ---

An Artificial Heme Enzyme for Cyclopropanation Reactions

Roelfes, G.

Angew. Chem., Int. Ed., 2018, 10.1002/anie.201802946


Metal: Fe
Ligand type: Protoporphyrin IX
Host protein: LmrR
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: 449
ee: 51
PDB: 6FUU
Notes: ---

An Artificial Imine Reductase Based on the Ribonuclease S Scaffold

Ward, T. R.

ChemCatChem, 2014, 10.1002/cctc.201300995


Metal: Ir
Ligand type: Amino acid; Cp*
Host protein: Ribonuclease S
Anchoring strategy: Supramolecular
Optimization: Genetic
Max TON: 4
ee: 18
PDB: ---
Notes: ---

An Artificial Metalloenzyme for Carbene Transfer Based on a Biotinylated Dirhodium Anchored Within Streptavidin

Ward, T. R.

Cat. Sci. Technol., 2018, 10.1039/C8CY00646F


Metal: Rh
Ligand type: Carboxylate
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: ~60
ee: ---
PDB: ---
Notes: Cyclopropanation reaction was also performed in the E. coli periplasm.

Metal: Rh
Ligand type: Carboxylate
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: C-H insertion
Max TON: ~60
ee: ---
PDB: ---
Notes: ---

An Artificial Oxygenase Built from Scratch: Substrate Binding Site Identified Using a Docking Approach

Cavazza, C.; Ménage, S.

Angew. Chem., Int. Ed., 2014, 10.1002/anie.201209021

The substrate for an artificial iron monooxygenase was selected by using docking calculations. The high catalytic efficiency of the reported enzyme for sulfide oxidation was directly correlated to the predicted substrate binding mode in the protein cavity, thus illustrating the synergetic effect of the substrate binding site, protein scaffold, and catalytic site.


Metal: Fe
Ligand type: BPMCN; BPMEN
Host protein: NikA
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Sulfoxidation
Max TON: 199
ee: ≤5
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: ---

An NAD(P)H-Dependent Artificial Transfer Hydrogenase for Multienzymatic Cascades

Ward, T. R.

J. Am. Chem. Soc., 2016, 10.1021/jacs.6b02470


Metal: Ir
Ligand type: Cp*; Phenanthroline
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: >999
ee: >99
PDB: ---
Notes: ---

A Noncanonical Proximal Heme Ligand Affords an Efficient Peroxidase in a Globin Fold

Green, A. P.; Hilvert, D.

J. Am. Chem. Soc., 2018, 10.1021/jacs.7b12621


Metal: Fe
Host protein: Myoglobin (Mb)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Oxidation
Max TON: ~1650
ee: ---
PDB: 5OJ9
Notes: Oxidation of amplex red

Antibody-Metalloporphyrin Catalytic Assembly Mimics Natural Oxidation Enzymes

Keinan, E.

J. Am. Chem. Soc., 1999, 10.1021/ja990314q


Metal: Ru
Ligand type: Porphyrin
Host protein: Antibody SN37.4
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Sulfoxidation
Max TON: 750
ee: 43
PDB: ---
Notes: ---

Aqueous Oxidation of Alcohols Catalyzed by Artificial Metalloenzymes Based on the Biotin–Avidin Technology

Ward, T. R.

J. Organomet. Chem., 2005, 10.1016/j.jorganchem.2005.02.001


Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Alcohol oxidation
Max TON: 200
ee: ---
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Avidin (Av)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Alcohol oxidation
Max TON: 230
ee: ---
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Bipyridine; C6Me6
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Alcohol oxidation
Max TON: 173
ee: ---
PDB: ---
Notes: ---

Metal: Rh
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Alcohol oxidation
Max TON: 7.5
ee: ---
PDB: ---
Notes: ---

Metal: Ir
Ligand type: Bipyridine; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Alcohol oxidation
Max TON: 30
ee: ---
PDB: ---
Notes: ---

Artificial Hydrogenases Based on Cobaloximes and Heme Oxygenase

Artero, V.

ChemPlusChem, 2016, 10.1002/cplu.201600218


Metal: Co
Ligand type: Oxime
Host protein: Heme oxygenase (HO)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: H2 evolution
Max TON: 15.3
ee: ---
PDB: ---
Notes: ---

Artificial Metalloenzyme for Enantioselective Sulfoxidation Based on Vanadyl-Loaded Streptavidin

Ward, T. R.

J. Am. Chem. Soc., 2008, 10.1021/ja8017219


Metal: V
Ligand type: Water
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Sulfoxidation
Max TON: 27
ee: 93
PDB: ---
Notes: ---

Artificial Metalloenzymes Based on Biotin-Avidin Technology for the Enantioselective Reduction of Ketones by Transfer Hydrogenation

Ward, T. R.

Proc. Natl. Acad. Sci. U. S. A., 2005, 10.1073/pnas.0409684102


Metal: Ru
Ligand type: Amino-sulfonamide; P-cymene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 92
ee: 94
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 30
ee: 63
PDB: ---
Notes: ---

Artificial Metalloenzymes Derived from Bovine β-Lactoglobulin for the Asymmetric Transfer Hydrogenation of an Aryl Ketone – Synthesis, Characterization and Catalytic Activity

Salmain, M.

Dalton Trans., 2014, 10.1039/c3dt53253d


Metal: Rh
Ligand type: Cp*; Poly-pyridine
Host protein: ß-lactoglobulin
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: 14
ee: 32
PDB: ---
Notes: ---

Artificial Metalloenzymes for Asymmetric Allylic Alkylation on the Basis of the Biotin–Avidin Technology

Ward, T. R.

Angew. Chem., Int. Ed., 2008, 10.1002/anie.200703159


Metal: Pd
Ligand type: Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Allylic alkylation
Max TON: 10
ee: 93
PDB: ---
Notes: ---

Artificial Metalloenzymes for Enantioselective Catalysis Based on Biotin-Avidin

Ward, T. R.

J. Am. Chem. Soc., 2003, 10.1021/ja035545i


Metal: Rh
Ligand type: Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Hydrogenation
Max TON: ---
ee: 96
PDB: ---
Notes: ---

Artificial Metalloenzymes for Enantioselective Catalysis: The Phenomenon of Protein Accelerated Catalysis

Ward, T. R.

J. Organomet. Chem., 2004, 10.1016/j.jorganchem.2004.09.032


Metal: Rh
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: ---
ee: 94
PDB: ---
Notes: Reduction of acetamidoacrylic acid. 3.0-fold protein acceleration.

Metal: Rh
Host protein: Avidin (Av)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: ---
ee: 39
PDB: ---
Notes: Reduction of acetamidoacrylic acid. 12.0-fold protein acceleration.

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

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: (Strept)avidin as Host for Enantioselective Hydrogenation by Achiral Biotinylated Rhodium-Diphosphine Complexes

Ward, T. R.

J. Am. Chem. Soc., 2004, 10.1021/ja0476718


Metal: Rh
Ligand type: Phosphine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Reaction: Hydrogenation
Max TON: ---
ee: 94
PDB: ---
Notes: ---

Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels–Alder Reaction

Mahy, J.-P.; Ricoux, R.

ChemBioChem, 2016, 10.1002/cbic.201500445


Metal: Cu
Ligand type: Phenanthroline
Anchoring strategy: Supramolecular
Optimization: ---
Max TON: 33
ee: ---
PDB: ---
Notes: Up to endo/exo ratio 62:38

Artificial Metalloproteins Containing Co4O4 Cubane Active Sites

Borovik, A. S.; Don Tilley, T.

J. Am. Chem. Soc., 2018, 10.1021/jacs.7b13052


Metal: Co
Ligand type: OAc; Pyridine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: ---
ee: ---
PDB: 6AUC
Notes: Co-complex in Sav WT

Metal: Co
Ligand type: OAc; Pyridine
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: ---
ee: ---
PDB: 6AUE
Notes: Co-complex in Sav S112Y

Artificial Peroxidase-Like Hemoproteins Based on Antibodies Constructed from a Specifically Designed Ortho-Carboxy Substituted Tetraarylporphyrin Hapten and Exhibiting a High Affinity for Iron-Porphyrins

Mahy, J.-P.

FEBS Lett., 1996, 10.1016/0014-5793(96)01006-X


Metal: Fe
Ligand type: Porphyrin
Host protein: Antibody 13G10
Anchoring strategy: Supramolecular
Optimization: ---
Max TON: ---
ee: ---
PDB: ---
Notes: kcat/KM = 105 M-1 * s-1

Artificial Transfer Hydrogenases Based on the Biotin-(Strept)avidin Technology: Fine Tuning the Selectivity by Saturation Mutagenesis of the Host Protein

Ward, T. R.

J. Am. Chem. Soc., 2006, 10.1021/ja061580o


Metal: Ir
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 96
ee: 80
PDB: ---
Notes: ---

Metal: Rh
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 73
ee: 60
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 95
ee: 70
PDB: ---
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; P-cymene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 79
ee: 97
PDB: ---
Notes: ---

Artificial Transfer Hydrogenases for the Enantioselective Reduction of Cyclic Imines

Ward, T. R.

Angew. Chem., Int. Ed., 2011, 10.1002/anie.201007820


Metal: Ir
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 4000
ee: 96
PDB: 3PK2
Notes: ---

Metal: Rh
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 94
ee: 52
PDB: 3PK2
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; P-cymene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 97
ee: 22
PDB: 3PK2
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 76
ee: 12
PDB: 3PK2
Notes: ---