11 publications

11 publications

An asymmetric catalyst

Akabori, S.; Sakurai, S.

Nature 1956, 178, 323-324, 10.1038/178323b0

Asymmetric synthesis has hitherto succeeded only by using reagents or solvents having the asymmetric configuration.


Metal: Pd
Ligand type: Undefined
Host protein: Silk fibroin fibre
Anchoring strategy: Undefined
Optimization: ---
Reaction: Hydrogenation
Max TON: >22
ee: ---
PDB: ---
Notes: ---

An Enantioselective Artificial Suzukiase Based on the Biotin–Streptavidin Technology

Ward, T.R.

Chem. Sci. 2016, 7, 673-677, 10.1039/c5sc03116h

Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee.


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 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 Metalloenzymes Through Cysteine-Selective Conjugation of Phosphines to Photoactive Yellow Protein

Kamer, P.C.J.

ChemBioChem 2010, 11, 1236-1239, 10.1002/cbic.201000159

Pinning phosphines on proteins: A method for the cysteine‐selective bioconjugation of phosphines has been developed. The photoactive yellow protein has been site‐selectively functionalized with phosphine ligands and phosphine transition metal complexes to afford artificial metalloenzymes that are active in palladium‐catalysed allylic nucleophilic substitution reactions.


Metal: Pd
Ligand type: Allyl; Phosphine
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: Allylic amination
Max TON: 45
ee: ---
PDB: 2PHY
Notes: ---

Atroposelective Antibodies as a Designed Protein Scaffold for Artificial Metalloenzymes

Harada, A.; Yamaguchi, H.

Sci. Rep. 2019, 9, 10.1038/s41598-019-49844-0

Design and engineering of protein scaffolds are crucial to create artificial metalloenzymes. Herein we report the first example of C-C bond formation catalyzed by artificial metalloenzymes, which consist of monoclonal antibodies (mAbs) and C2 symmetric metal catalysts. Prepared as a tailored protein scaffold for a binaphthyl derivative (BN), mAbs bind metal catalysts bearing a 1,1?-bi-isoquinoline (BIQ) ligand to yield artificial metalloenzymes. These artificial metalloenzymes catalyze the Friedel-Crafts alkylation reaction. In the presence of mAb R44E1, the reaction proceeds with 88% ee. The reaction catalyzed by Cu-catalyst incorporated into the binding site of mAb R44E1 is found to show excellent enantioselectivity with 99% ee. The protein environment also enables the use of BIQ-based catalysts as asymmetric catalysts for the first time.


Metal: Cu; Pd; Pt
Ligand type: Bipyridine
Host protein: Antibody
Anchoring strategy: Antigen
Optimization: Genetic
Max TON: 2
ee: 88
PDB: ---
Notes: ---

Control of the Coordination Structure of Organometallic Palladium Complexes in an Apo-Ferritin Cage

Ueno, T.; Watanabe, Y.

J. Am. Chem. Soc. 2008, 130, 10512-10514, 10.1021/ja802463a

We report the preparation of organometallic Pd(allyl) dinuclear complexes in protein cages of apo-Fr by reactions with [Pd(allyl)Cl]2 (allyl = η3-C3H5). One of the dinuclear complexes is converted to a trinuclear complex by replacing a Pd-coordinated His residue to an Ala residue. These results suggest that multinuclear metal complexes with various coordination structures could be prepared by the deletion or introduction of His, Cys, and Glu at appropriate positions on protein surface.


Metal: Pd
Ligand type: Allyl
Host protein: Ferritin
Anchoring strategy: Dative
Optimization: ---
Reaction: Suzuki coupling
Max TON: ---
ee: ---
PDB: 2ZG7
Notes: ---

Definite Coordination Arrangement of Organometallic Palladium Complexes Accumulated on the Designed Interior Surface of Apo-Ferritin

Ueno, T.

Chem. Commun. 2011, 47, 170-172, 10.1039/C0CC02221G

Apo-ferritin (apo-Fr) mutants are used as scaffolds to accommodate palladium (allyl) complexes. Various coordination arrangements of the Pd complexes are achieved by adjusting the positions of cysteine and histidine residues on the interior surface of the apo-Fr cage.


Metal: Pd
Ligand type: Allyl
Host protein: Ferritin
Anchoring strategy: Dative
Optimization: Genetic
Reaction: Suzuki coupling
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Immobilization of Two Organometallic Complexes into a Single Cage to Construct Protein-Based Microcompartment

Ueno, T.

Chem. Commun. 2016, 52, 5463-5466, 10.1039/C6CC00679E

Natural protein-based microcompartments containing multiple enzymes promote cascade reactions within cells. We use the apo-ferritin protein cage to mimic such biocompartments by immobilizing two organometallic Ir and Pd complexes into the single protein cage. Precise locations of the metals and their accumulation mechanism were studied by X-ray crystallography.


Metal: Ir
Ligand type: Amino acid; Cp*
Host protein: Apo-ferritin
Anchoring strategy: Dative
Optimization: Chemical
Reaction: Hydrogenation
Max TON: ~2
ee: 15
PDB: 5E2D
Notes: Tandem reaction (Hydrogenation and Suzuki-Miyaura coupling) to form biphenylethanol from 4-iodoacetophenone and phenylboronic acid. TON and ee are given for the tandem reaction product.

Metal: Pd
Ligand type: Allyl; Amino acid
Host protein: Apo-ferritin
Anchoring strategy: Dative
Optimization: Chemical
Max TON: ~1
ee: 15
PDB: 5E2D
Notes: Tandem reaction (Hydrogenation and Suzuki-Miyaura coupling) to form biphenylethanol from 4-iodoacetophenone and phenylboronic acid.

Preparation of an Immobilized Lipase-Palladium Artificial Metalloenzyme as Catalyst in the Heck Reaction: Role of the Solid Phase

Filice, M.; Palomo, J.M.

Adv. Synth. Catal. 2015, 357, 2687-2696, 10.1002/adsc.201500014

A p‐nitrophenylphosphonate palladium pincer was synthesized and selectively inserted by irreversible attachment on the catalytic serine of different commercial lipases with good to excellent yields in most cases. Among all, lipase from Candida antarctica B (CAL‐B) was the best modified enzyme. The artificial metalloenzyme CAL‐B‐palladium (Pd) catalyst was subsequently immobilized on different supports and by different orienting strategies. The catalytic properties of the immobilized hybrid catalysts were then evaluated in two sets of Heck cross‐coupling reactions under different conditions. In the first reaction between iodobenzene and ethyl acrylate, the covalent immobilized CAL‐B‐Pd catalyst resulted to be the best one exhibiting quantitative production of the Heck product at 70 °C in dimethylformamide (DMF) with 25% water and particularly in pure DMF, where the soluble Pd pincer was completely inactive. A post‐immobilization engineering of catalyst surface by its hydrophobization enhanced the activity. The selectivity properties of the best hybrid catalyst were then assessed in the asymmetric Heck cross‐coupling reaction between iodobenzene and 2,3‐dihydrofuran retrieving excellent results in terms of stereo‐ and enantioselectivity.


Metal: Pd
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Max TON: ~4160
ee: 96
PDB: ---
Notes: ArM is immobilized on Sepabeads.

Robust and Versatile Hos Protein for the Design and Evaluation of Artificial Metal Centers

Arold, S.T.; Eppinger, J.; Groll, M.

ACS Catal. 2019, 9, 11371-11380, 10.1021/acscatal.9b02896

Artificial metalloenzymes (ArMs) have high potential in biotechnological applications as they combine the versatility of transition-metal catalysis with the substrate selectivity of enzymes. An ideal host protein should allow high-yield recombinant expression, display thermal and solvent stability to withstand harsh reaction conditions, lack nonspecific metal-binding residues, and contain a suitable cavity to accommodate the artificial metal site. Moreover, to allow its rational functionalization, the host should provide an intrinsic reporter for metal binding and structural changes, which should be readily amendable to high-resolution structural characterization. Herein, we present the design, characterization, and de novo functionalization of a fluorescent ArM scaffold, named mTFP*, that achieves these characteristics. Fluorescence measurements allowed direct assessment of the scaffold’s structural integrity. Protein X-ray structures and transition metal Förster resonance energy transfer (tmFRET) studies validated the engineered metal coordination sites and provided insights into metal binding dynamics at the atomic level. The implemented active metal centers resulted in ArMs with efficient Diels–Alderase and Friedel–Crafts alkylase activities.


Metal: Cu; Ni; Pd; Rh
Ligand type: ---
Host protein: Monomeric Teal FP (mTFP)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: ---
ee: ---
PDB: ---
Notes: Also Friedel–Crafts alkylation

Supramolecular Anchoring of NCN-Pincer Palladium Complexes into a β-Barrel Protein Host: Molecular-Docking and Reactivity Insights

Salmain, M.; Thorimbert, S.

Eur. J. Inorg. Chem. 2017, 2017, 3622-3634, 10.1002/ejic.201700365

Several prochiral NCN‐pincer complexes of palladium(II), with hemilabile ligands and a long aliphatic chain, were synthesized and characterized spectroscopically. In some of the complexes, the presence of two different substituents on the N donor atoms made them stereogenic, so that they were isolated as a mixture of diastereoisomers, which could be differentiated by 1H NMR spectroscopy. Binding of some of these complexes to bovine β‐lactoglobin by insertion within its inner cavity was theoretically investigated by molecular‐docking simulations and was experimentally confirmed by CD spectroscopy. Adjunction of H‐bond donor substituents on the ligand framework gave more‐stable supramolecular protein–complex assemblies. These constructs were shown to catalyze aldol condensation reactions in aqueous media, affording, in some cases, the less‐favorable cis product. Since the corresponding complexes exclusively gave the trans product in the absence of β‐lactoglobulin, this unusual diastereoselectivity was ensued by the second sphere of coordination brought by the protein host.


Metal: Pd
Ligand type: NCN-Pincer (amines)
Host protein: β-lactoglobulin (βLG)
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Aldol condensation
Max TON: 4.9
ee: 0
PDB: ---
Notes: Aldol condensation of methyl isocyanoacetate and benzaldehyde (trans/cis = 38:62)