9 publications

9 publications

A General Method for Artificial Metalloenzyme Formationthrough Strain-Promoted Azide–Alkyne Cycloaddition

Lewis, J.C.

ChemBioChem 2014, 15, 223-227, 10.1002/cbic.201300661

Strain‐promoted azide–alkyne cycloaddition (SPAAC) can be used to generate artificial metalloenzymes (ArMs) from scaffold proteins containing a p‐azido‐L‐phenylalanine (Az) residue and catalytically active bicyclononyne‐substituted metal complexes. The high efficiency of this reaction allows rapid ArM formation when using Az residues within the scaffold protein in the presence of cysteine residues or various reactive components of cellular lysate. In general, cofactor‐based ArM formation allows the use of any desired metal complex to build unique inorganic protein materials. SPAAC covalent linkage further decouples the native function of the scaffold from the installation process because it is not affected by native amino acid residues; as long as an Az residue can be incorporated, an ArM can be generated. We have demonstrated the scope of this method with respect to both the scaffold and cofactor components and established that the dirhodium ArMs generated can catalyze the decomposition of diazo compounds and both SiH and olefin insertion reactions involving these carbene precursors.


Metal: Rh
Ligand type: Poly-carboxylic acid
Host protein: tHisF
Anchoring strategy: Covalent
Optimization: ---
Reaction: Cyclopropanation
Max TON: 81
ee: ---
PDB: 1THF
Notes: ---

Metal: Rh
Ligand type: Poly-carboxylic acid
Host protein: tHisF
Anchoring strategy: Covalent
Optimization: ---
Reaction: Si-H insertion
Max TON: 7
ee: ---
PDB: 1THF
Notes: ---

Artificial Metalloenzymes for Enantioselective Catalysis: Recent Advances

Review

Ward, T.R.

ChemBioChem 2006, 7, 1845-1852, 10.1002/cbic.200600264

Creating new catalytic function in proteins. Anchoring an organometallic moiety within a protein affords artificial metalloenzymes for enantioselective catalysis. Both chemical and genetic tools can be applied in the optimization of such systems, which lie at the interface between homogeneous and enzymatic catalysis. This minireview presents the latest developments in the field of artificial metalloenzymes.


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: ---

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

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

ChemBioChem 2016, 17, 433-440, 10.1002/cbic.201500445

A new artificial enzyme formed by associating NCS‐3.24 with a copper complex catalyzed the Diels–Alder cyclization of cyclopentadiene with 2‐azachalcone and led to an increase in the formation of the exo‐products. Molecular modeling proposed the preferred relative positioning of both the Trojan horse complex and the two substrates.


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

Incorporation of Manganese Complexes into Xylanase: New Artificial Metalloenzymes for Enantioselective Epoxidation

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

ChemBioChem 2012, 13, 240-251, 10.1002/cbic.201100659

Enantioselective epoxidation: An artificial metalloenzyme obtained by noncovalent insertion of MnIII‐meso‐tetrakis(para‐carboxyphenyl)porphyrin Mn(TpCPP) into xylanase 10A from Streptomyces lividans as a host protein was able to catalyse the oxidation of para‐methoxystyrene by KHSO5 with a 16 % yield and the best enantioselectivity (80 % in favour of the R isomer) ever reported for an artificial metalloenzyme.


Metal: Mn
Ligand type: Porphyrin
Host protein: Xylanase A (XynA)
Anchoring strategy: Supramolecular
Optimization: ---
Reaction: Epoxidation
Max TON: 21
ee: 80
PDB: ---
Notes: ---

Orthogonal Expression of an Artificial Metalloenzyme for Abiotic Catalysis

Brustad, E.M.

ChemBioChem 2017, 18, 2380-2384, 10.1002/cbic.201700397

Engineering an (Ir)regular cytochrome P450: Mutations within the heme‐binding pocket of a cytochrome P450 enabled the selective incorporation of an artificial Ir‐porphyrin cofactor into the protein, in cells. This orthogonal metalloprotein showed enhanced behavior in unnatural carbene‐mediated cyclopropanation of aliphatic and electron‐deficient olefins.


Metal: Ir
Ligand type: Methyl; Porphyrin
Host protein: Cytochrome BM3h
Anchoring strategy: Reconstitution
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: 339
ee: 97
PDB: ---
Notes: Reaction of styrene with ethyl diazoacetate, cis:trans = 29:71

Polymer Enzyme Conjugates as Chiral Ligands for Sharpless Dihydroxylation of Alkenes in Organic Solvents

Tiller, J.C.

ChemBioChem 2015, 16, 83-90, 10.1002/cbic.201402339

Count Os in: We report organosoluble artificial metalloenzymes, generated from poly(2‐methyl‐oxazoline) enzyme conjugates and osmate as a promising new catalytic system for the dihydroxylation of alkenes in organic media.


Metal: Os
Ligand type: Amino acid
Host protein: Laccase
Anchoring strategy: Metal substitution
Optimization: Chemical
Reaction: Dihydroxylation
Max TON: 80
ee: 98
PDB: ---
Notes: ---

The Protein Environment Drives Selectivity for Sulfide Oxidation by an Artificial Metalloenzyme

Cavazza, C.; Ménage, S.

ChemBioChem 2009, 10, 545-552, 10.1002/cbic.200800595

Magic Mn–salen metallozyme: The design of an original, artificial, inorganic, complex‐protein adduct, has led to a better understanding of the synergistic effects of both partners. The exclusive formation of sulfoxides by the hybrid biocatalyst, as opposed to sulfone in the case of the free inorganic complex, highlights the modulating role of the inorganic‐complex‐binding site in the protein.


Metal: Mn
Ligand type: Salen
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Sulfoxidation
Max TON: 97
ee: ---
PDB: ---
Notes: ---

Transforming Carbonic Anhydrase into Epoxide Synthase by Metal Exchange

Soumillion, P.

ChemBioChem 2006, 7, 1013-1016, 10.1002/cbic.200600127

Enantioselective epoxidation of styrene was observed in the presence of manganese‐containing carbonic anhydrase as catalyst. The probable oxygen‐transfer reagent is peroxymonocarbonate, which has a structural similarity with the hydrogenocarbonate substrate of the natural reaction. Styrene was chosen as the enzyme possesses a small hydrophobic cavity close to the active site.


Metal: Mn
Ligand type: Amino acid
Anchoring strategy: Metal substitution
Optimization: Chemical & genetic
Reaction: Epoxidation
Max TON: 4.1
ee: 52
PDB: ---
Notes: ---

Metal: Mn
Ligand type: Amino acid
Anchoring strategy: Metal substitution
Optimization: Chemical & genetic
Reaction: Epoxidation
Max TON: 10.3
ee: 40
PDB: ---
Notes: ---