24 publications

24 publications

A Chaperonin as Protein Nanoreactor for Atom-Transfer Radical Polymerization

Bruns, N.

Angew. Chem., Int. Ed., 2013, 10.1002/anie.201306798

The group II chaperonin thermosome (THS) from the archaea Thermoplasma acidophilum is reported as nanoreactor for atom‐transfer radical polymerization (ATRP). A copper catalyst was entrapped into the THS to confine the polymerization into this protein cage. THS possesses pores that are wide enough to release polymers into solution. The nanoreactor favorably influenced the polymerization of N‐isopropyl acrylamide and poly(ethylene glycol)methylether acrylate. Narrowly dispersed polymers with polydispersity indices (PDIs) down to 1.06 were obtained in the protein nanoreactor, while control reactions with a globular protein–catalyst conjugate only yielded polymers with PDIs above 1.84.


Metal: Cu
Host protein: Thermosome (THS)
Anchoring strategy: Covalent
Optimization: ---
Reaction: Polymerization
Max TON: ---
ee: ---
PDB: ---
Notes: Non-ROMP

A De Novo Designed Metalloenzyme for the Hydration of CO2

Pecoraro, V. L.

Angew. Chem., Int. Ed., 2014, 10.1002/anie.201404925

Protein design will ultimately allow for the creation of artificial enzymes with novel functions and unprecedented stability. To test our current mastery of nature’s approach to catalysis, a ZnII metalloenzyme was prepared using de novo design. α3DH3 folds into a stable single‐stranded three‐helix bundle and binds ZnII with high affinity using His3O coordination. The resulting metalloenzyme catalyzes the hydration of CO2 better than any small molecule model of carbonic anhydrase and with an efficiency within 1400‐fold of the fastest carbonic anhydrase isoform, CAII, and 11‐fold of CAIII.


Metal: Zn
Ligand type: Amino acid
Host protein: α3D peptide
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: ---
ee: ---
PDB: ---
Notes: kcat/KM ≈ 3.8*104 M-1*s-1

A Designed Functional Metalloenzyme that Reduces O2 to H2O with Over One Thousand Turnovers

Lu, Y.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201201981

Rational design of functional enzymes with a high number of turnovers is a challenge, especially those with a complex active site, such as respiratory oxidases. Introducing two His and one Tyr residues into myoglobin resulted in enzymes that reduce O2 to H2O with more than 1000 turnovers (red line, see scheme) and minimal release of reactive oxygen species. The positioning of the Tyr residue is critical for activity.


Metal: Cu
Ligand type: Amino acid
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: 1056
ee: ---
PDB: 4FWX
Notes: Sperm whale myoglobin

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 Metalloenzyme: Creation of a Designed Copper Binding Site in a Thermostable Protein

Reetz, M. T.

Angew. Chem., Int. Ed., 2010, 10.1002/anie.201002106

Guided by nature: A designed binding site comprising the His/His/Asp motif for CuII complexation has been constructed in a robust protein by site‐specific mutagenesis (see picture). The artificial metalloenzyme catalyzes an enantioselective Diels–Alder reaction.


Metal: Cu
Ligand type: Amino acid
Host protein: tHisF
Anchoring strategy: Dative
Optimization: Genetic
Max TON: 6.7
ee: 46
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: ---

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 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: ---

Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties

Albrecht, M.; Paradisi, F.

Angew. Chem., Int. Ed., 2018, 10.1002/ange.201807168


Metal: Cu
Host protein: Azurin
Anchoring strategy: Dative
Optimization: Chemical & genetic
Reaction: Electron transfer
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Copper–Phthalocyanine Conjugates of Serum Albumins as Enantioselective Catalysts in Diels–Alder Reactions

Reetz, M. T.

Angew. Chem., Int. Ed., 2005, 10.1002/anie.200504561


Metal: Cu
Ligand type: Phthalocyanine
Anchoring strategy: Supramolecular
Optimization: Chemical
Max TON: 45.5
ee: 98
PDB: ---
Notes: ---

Cross-Regulation of an Artificial Metalloenzyme

Ward, T. R.

Angew. Chem., Int. Ed., 2017, 10.1002/anie.201702181


Metal: Ir
Ligand type: Cp*; Phenanthroline
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 96
ee: ---
PDB: ---
Notes: Cross-regulated reduction of the antibiotic enrofloxacin by an ArM.

Directed Evolution of an Artificial Imine Reductase

Maréchal, J.-D.; Ward, T. R.

Angew. Chem., Int. Ed., 2018, 10.1002/anie.201711016


Metal: Ir
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 380
ee: 95
PDB: 6ESS
Notes: Salsolidine formation; Sav mutant S112A-N118P-K121A-S122M: (R)-selective

Metal: Ir
Ligand type: Amino-sulfonamide; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 220
ee: 85
PDB: 6ESU
Notes: Salsolidine formation; Sav mutant S112R-N118P-K121A-S122M-L124Y: (S)-selective

Directed Evolution of Iridium-Substituted Myoglobin Affords Versatile Artificial Metalloenzymes for Enantioselective C-C Bond-Forming Reactions

Review

Ward, T. R.

Angew. Chem., Int. Ed., 2016, 10.1002/anie.201607222


Notes: ---

Enantioselective Artificial Metalloenzymes by Creation of a Novel Active Site at the Protein Dimer Interface

Roelfes, G.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201202070


Metal: Cu
Ligand type: Bipyridine; Phenanthroline
Host protein: LmrR
Anchoring strategy: Covalent
Optimization: Genetic
Max TON: 32.7
ee: 97
PDB: 3F8B
Notes: ---

Enzyme Activity by Design: An Artificial Rhodium Hydroformylase for Linear Aldehydes

Jarvis, A. G.; Kamer, P. C. J.

Angew. Chem., Int. Ed., 2017, 10.1002/ange.201705753


Metal: Rh
Ligand type: Acac; Diphenylphosphine
Anchoring strategy: Cystein-maleimide
Optimization: Chemical & genetic
Reaction: Hydroformylation
Max TON: 409
ee: ---
PDB: ---
Notes: Selectivity for the linear product over the branched product

Genetic Optimization of Metalloenzymes: Enhancing Enzymes for Non-Natural Reactions

Review

Hyster, T. K.; Ward, T. R.

Angew. Chem., Int. Ed., 2016, 10.1002/anie.201508816


Notes: ---

Metal-Mediated Functionalization of Natural Peptides and Proteins: Panning for Bioconjugation Gold

Review

Ball, Z. T.

Angew. Chem., Int. Ed., 2019, 10.1002/anie.201807536


Notes: ---

OsO4·Streptavidin: A Tunable Hybrid Catalyst for the Enantioselective cis-Dihydroxylation of Olefins

Ward, T. R.

Angew. Chem., Int. Ed., 2011, 10.1002/anie.201103632


Metal: Os
Ligand type: Undefined
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: Dihydroxylation
Max TON: 16
ee: 97
PDB: ---
Notes: ---

Preparation of Artificial Metalloenzymes by Insertion of Chromium(III) Schiff Base Complexes into apo-Myoglobin Mutants

Watanabe, Y.

Angew. Chem., Int. Ed., 2003, 10.1002/anie.200390256


Metal: Cr
Ligand type: Salophen
Host protein: Myoglobin (Mb)
Anchoring strategy: Reconstitution
Optimization: Genetic
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Significant Increase of Oxidase Activity through the Genetic Incorporation of a Tyrosine–Histidine Cross-Link in a Myoglobin Model of Heme–Copper Oxidase

Lu, Y.; Wang, J.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201108756


Metal: Cu
Ligand type: Amino acid
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: 1100
ee: ---
PDB: ---
Notes: Sperm whale myoglobin

Tailoring the Active Site of Chemzymes by Using a Chemogenetic-Optimization Procedure: Towards Substrate-Specific Artificial Hydrogenases Based on the Biotin–Avidin Technology

Ward, T. R.

Angew. Chem., Int. Ed., 2005, 10.1002/anie.200502000


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

Towards Evolution of Artificial Metalloenzymes - A Protein Engineer’s Perspective

Review

Schwaneberg, U.

Angew. Chem., Int. Ed., 2018, 10.1002/anie.201811042


Notes: ---

Upregulation of an Artificial Zymogen by Proteolysis

Ward, T. R.

Angew. Chem., Int. Ed., 2016, 10.1002/anie.201605010


Metal: Ir
Ligand type: Cp*; Tripeptide
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 2000
ee: 73
PDB: ---
Notes: ---

X-Ray Structure and Designed Evolution of an Artificial Transfer Hydrogenase

Ward, T. R.

Angew. Chem., Int. Ed., 2008, 10.1002/anie.200704865


Metal: Ru
Ligand type: Amino-sulfonamide; Benzene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 100
ee: 92
PDB: 2QCB
Notes: ---

Metal: Ru
Ligand type: Amino-sulfonamide; P-cymene
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: 97
ee: 96
PDB: 2QCB
Notes: ---