27 publications

27 publications

A Chaperonin as Protein Nanoreactor for Atom-Transfer Radical Polymerization

Bruns, N.

Angew. Chem. Int. Ed. 2014, 53, 1443-1447, 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, 53, 7900-7903, 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, 51, 5589-5592, 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, 57, 7785-7789, 10.1002/anie.201802946

An artificial heme enzyme was created through self‐assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre‐catalytic structures.


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, 49, 5151-5155, 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. 2013, 52, 3922-3925, 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, 47, 701-705, 10.1002/anie.200703159

Palladium in the active site: The incorporation of a biotinylated palladium diphosphine within streptavidin yielded an artificial metalloenzyme for the title reaction (see scheme). Chemogenetic optimization of the catalyst by the introduction of a spacer (red star) between biotin (green triangle) and palladium and saturation mutagenesis at position S112X afforded both R‐ and S‐selective artificial asymmetric allylic alkylases.


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, 50, 3026-3029, 10.1002/anie.201007820

Man‐made activity: Introduction of a biotinylated iridium piano stool complex within streptavidin affords an artificial imine reductase (see scheme). Saturation mutagenesis allowed optimization of the activity and the enantioselectivity of this metalloenzyme, and its X‐ray structure suggests that a nearby lysine residue acts as a proton source during the transfer hydrogenation.


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, 130, 10837-10842, 10.1002/ange.201807168

Im Tausch gegen NHC: Die Einfügung eines N‐heterocyclischen Carbenliganden (grün/blau) als Ersatz für His in das aktive Zentrum des Redoxenzyms Azurin rekonstituiert das T1‐Kupferzentrum. Der resultierende Komplex ist spektroskopisch kaum unterscheidbar von der N‐Bindung von His oder N‐Methylimidazol, senkt aber signifikant das Reduktionspotential des Kupferzentrums und erleichtert dadurch Elektronentransferprozesse.


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. 2006, 45, 2416-2419, 10.1002/anie.200504561

Chirality from blood: Serum albumins form strong complexes with CuII–phthalocyanines, leading to protein conjugates. These hybrid catalysts promote enantioselective Diels–Alder reactions, such as that of azachalcones 1 with cyclopentadiene (2) to give products 3 with 85–98 % ee.


Metal: Cu
Ligand type: Phthalocyanine
Anchoring strategy: Supramolecular
Optimization: Chemical
Max TON: 45.5
ee: 98
PDB: ---
Notes: Chirality from blood: Serum albumins form strong complexes with CuII–phthalocyanines, leading to protein conjugates. These hybrid catalysts promote enantioselective Diels–Alder reactions, such as that of azachalcones 1 with cyclopentadiene (2) to give products 3 with 85–98 % ee.

Cross-Regulation of an Artificial Metalloenzyme

Ward, T.R.

Angew. Chem. Int. Ed. 2017, 56, 10156-10160, 10.1002/anie.201702181

Cross‐regulation of complex biochemical reaction networks is an essential feature of living systems. In a biomimetic spirit, we report on our efforts to program the temporal activation of an artificial metalloenzyme via cross‐regulation by a natural enzyme. In the presence of urea, urease slowly releases ammonia that reversibly inhibits an artificial transfer hydrogenase. Addition of an acid, which acts as fuel, allows to maintain the system out of equilibrium.


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, 57, 1863-1868, 10.1002/anie.201711016

Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin‐streptavidin technology using a straightforward procedure allowing screening in cell‐free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X‐ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein–ligand dockings.


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, 55, 14909-14911, 10.1002/anie.201607222

Upgrading myoglobin with iridium: A metal‐substitution strategy has been used to afford a repurposed myoglobin for challenging cyclopropanation and intramolecular C−H activation reactions. The performance of the iridium‐loaded myoglobin (orange sphere) was improved through directed evolution of eight active‐site residues (yellow surface).


Notes: ---

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

Roelfes, G.

Angew. Chem. Int. Ed. 2012, 51, 7472-7475, 10.1002/anie.201202070

A game of two halves: Artificial metalloenzymes are generated by forming a novel active site on the dimer interface of the transcription factor LmrR. Two copper centers are incorporated by binding to ligands in each half of the dimer. With this system up to 97 % ee was obtained in the benchmark CuII catalyzed Diels–Alder reaction (see scheme).


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, 129, 13784-13788, 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, 55, 7344-7357, 10.1002/anie.201508816

Artificial metalloenzymes have received increasing attention over the last decade as a possible solution to unaddressed challenges in synthetic organic chemistry. Whereas traditional transition‐metal catalysts typically only take advantage of the first coordination sphere to control reactivity and selectivity, artificial metalloenzymes can modulate both the first and second coordination spheres. This difference can manifest itself in reactivity profiles that can be truly unique to artificial metalloenzymes. This Review summarizes attempts to modulate the second coordination sphere of artificial metalloenzymes by using genetic modifications of the protein sequence. In doing so, successful attempts and creative solutions to address the challenges encountered are highlighted.


Notes: ---

Highly Efficient Cyclic Dinucleotide Based Artificial Metalloribozymes for Enantioselective Friedel–Crafts Reactions in Water

Chen, Y.; Wang, C.

Angew. Chem. Int. Ed. 2020, 59, 3444-3449, 10.1002/anie.201912962

The diverse secondary structures of nucleic acids are emerging as attractive chiral scaffolds to construct artificial metalloenzymes (ArMs) for enantioselective catalysis. DNA‐based ArMs containing duplex and G‐quadruplex scaffolds have been widely investigated, yet RNA‐based ArMs are scarce. Here we report that a cyclic dinucleotide of c‐di‐AMP and Cu2+ ions assemble into an artificial metalloribozyme (c‐di‐AMP⋅Cu2+) that enables catalysis of enantioselective Friedel–Crafts reactions in aqueous media with high reactivity and excellent enantioselectivity of up to 97 % ee. The assembly of c‐di‐AMP⋅Cu2+ gives rise to a 20‐fold rate acceleration compared to Cu2+ ions. Based on various biophysical techniques and density function theory (DFT) calculations, a fine coordination structure of c‐di‐AMP⋅Cu2+ metalloribozyme is suggested in which two c‐di‐AMP form a dimer scaffold and the Cu2+ ion is located in the center of an adenine‐adenine plane through binding to two N7 nitrogen atoms and one phosphate oxygen atom.


Metal: Cu
Ligand type: RNA
Host protein: RNA
Anchoring strategy: Dative
Optimization: Chemical
Max TON: 20
ee: 97
PDB: ---
Notes: ---

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

Review

Ball, Z.T.

Angew. Chem. Int. Ed. 2019, 58, 6176-6199, 10.1002/anie.201807536

Selective modification of natural proteins is a daunting methodological challenge and a stringent test of selectivity and reaction scope. There is a continued need for new reactivity and new selectivity concepts. Transition metals exhibit a wealth of unique reactivity that is orthogonal to biological reactions and processes. As such, metal?based methods play an increasingly important role in bioconjugation. This Review examines metal?based methods as well as their reactivity and selectivity for the functionalization of natural proteins and peptides.


Notes: ---

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

Ward, T.R.

Angew. Chem. Int. Ed. 2011, 50, 10863-10866, 10.1002/anie.201103632

Taking control: Selective catalysts for olefin dihydroxylation have been generated by the combination of apo‐streptavidin and OsO4. Site‐directed mutagenesis allows improvement of enantioselectivity and even inversion of enantiopreference in certain cases. Notably allyl phenyl sulfide and cis‐β‐methylstyrene were converted with unprecedented enantiomeric excess.


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, 42, 1005-1008, 10.1002/anie.200390256

Insertion of a symmetric metal complex, [CrIII(5,5′‐tBu‐salophen)]+ (H2salophen=N,N′‐bis(salicylidene)‐1,2‐phenylenediamine), into the active site of apomyoglobin is demonstrated (see picture). The metal ion and the ligand structure are very important factors that influence the binding affinity of the metal complex with the myoglobin (Mb) cavity. Semisynthetic metalloenzymes can catalyze enantioselective sulfoxidation by using the chiral protein cavity.


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

Regulating Transition Metal Catalysis Through Interference by Short RNAs

Nelson, H.M.

Angew. Chem. Int. Ed. 2019, 58, 16400-16404, 10.1002/anie.201905333

Herein we report the discovery of a AuI–DNA hybrid catalyst that is compatible with biological media and whose reactivity can be regulated by small complementary nucleic acid sequences. The development of this catalytic system was enabled by the discovery of a novel AuI‐mediated base pair. We found that AuI binds DNA containing C‐T mismatches. In the AuI–DNA catalyst's latent state, the AuI ion is sequestered by the mismatch such that it is coordinatively saturated, rendering it catalytically inactive. Upon addition of an RNA or DNA strand that is complementary to the latent catalyst's oligonucleotide backbone, catalytic activity is induced, leading to a sevenfold increase in the formation of a fluorescent product, forged through a AuI‐catalyzed hydroamination reaction. Further development of this catalytic system will expand not only the chemical space available to synthetic biological systems but also allow for temporal and spatial control of transition‐metal catalysis through gene transcription.


Metal: Au
Ligand type: C-T mismatch
Host protein: DNA
Anchoring strategy: Dative
Optimization: ---
Reaction: Hydroamination
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, 51, 4312-4316, 10.1002/anie.201108756

Top model: Heme–copper oxidase (HCO) contains a histidine–tyrosine cross‐link in its heme a3/CuB oxygen reduction center. A functional model of HCO was obtained through the genetic incorporation of the unnatural amino acid imiTyr, which mimics the Tyr–His cross‐link, and of the CuB site into myoglobin (see picture). Like HCO, this small soluble protein exhibits selective O2‐reduction activity while generating little reactive oxygen species.


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

Site‐Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium‐Porphyrin Cofactor

Hartwig, J.F.

Angew. Chem. Int. Ed. 2019, 58, 13954-13960, 10.1002/anie.201907460

The selective functionalization of one C-H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site-selective functionalizations of C-H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium-porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C-H bonds of arange of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site-selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C-H bonds with site selectivity that is difficult to achieve with small-molecule catalysts.


Metal: Ir
Ligand type: Porphyrin
Host protein: Cytochrome P450 (CYP119)
Anchoring strategy: Reconstitution
Optimization: Genetic
Max TON: 2286
ee: 94
PDB: ---
Notes: ---

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, 44, 7764-7767, 10.1002/anie.200502000

The combination of chemical‐ with genetic‐optimization strategies (i.e. chemogenetic) allows the production of artificial hydrogenases based on the biotin–avidin technology. In the spirit of enzymes, second‐coordination‐sphere interactions between the host protein (streptavidin) and the substrate (an olefin) allow fine‐tuning of the selectivity to produce either R or S hydrogenation products.


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. 2019, 58, 4454-4464, 10.1002/anie.201811042

Incorporating artificial metal‐cofactors into protein scaffolds results in a new class of catalysts, termed biohybrid catalysts or artificial metalloenzymes. Biohybrid catalysts can be modified chemically at the first coordination sphere of the metal complex, as well as at the second coordination sphere provided by the protein scaffold. Protein‐scaffold reengineering by directed evolution exploits the full power of nature's diversity, but requires validated screening and sophisticated metal cofactor conjugation to evolve biohybrid catalysts. In this Minireview, we summarize the recent efforts in this field to establish high‐throughput screening methods for biohybrid catalysts and we show how non‐chiral catalysts catalyze reactions enantioselectively by highlighting the first successes in this emerging field. Furthermore, we shed light on the potential of this field and challenges that need to be overcome to advance from biohybrid catalysts to true artificial metalloenzymes.


Notes: ---

Upregulation of an Artificial Zymogen by Proteolysis

Ward, T.R.

Angew. Chem. Int. Ed. 2016, 55, 11587-11590, 10.1002/anie.201605010

Regulation of enzymatic activity is vital to living organisms. Here, we report the development and the genetic optimization of an artificial zymogen requiring the action of a natural protease to upregulate its latent asymmetric transfer hydrogenase activity.


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, 47, 1400-1404, 10.1002/anie.200704865

A structure is worth a thousand words: Guided by the X‐ray structure of an S‐selective artificial transfer hydrogenase, designed evolution was used to optimize the selectivity of hybrid catalysts. Fine‐tuning of the second coordination sphere of the ruthenium center (see picture, orange sphere) by introduction of two point mutations allowed the identification of selective artificial transfer hydrogenases for the reduction of dialkyl ketones.


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: ---