10 publications

10 publications

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

Lewis, J. C.

ChemBioChem, 2014, 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 and Metallopeptide Catalysts for Organic Synthesis

Review

Lewis, J. C.

ACS Catal., 2013, 10.1021/cs400806a


Notes: ---

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies

Review

Lewis, J. C.; Ward, T. R.

Chem. Rev., 2018, 10.1021/acs.chemrev.7b00014


Notes: ---

Beyond the Second Coordination Sphere: Engineering Dirhodium Artificial Metalloenzymes To Enable Protein Control of Transition Metal Catalysis

Review

Lewis, J. C.

Acc. Chem. Res., 2019, 10.1021/acs.accounts.8b00625


Notes: ---

Engineering a Dirhodium Artificial Metalloenzyme for Selective Olefin Cyclopropanation

Lewis, J. C.

Nat. Commun., 2015, 10.1038/ncomms8789


Metal: Rh
Ligand type: Poly-carboxylic acid
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: 74
ee: 92
PDB: ---
Notes: ---

Evolving Artificial Metalloenzymes via Random Mutagenesis

Lewis, J. C.

Nat. Chem., 2018, 10.1038/nchem.2927


Metal: Rh
Ligand type: OAc
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: Cyclopropanation
Max TON: 66
ee: 94
PDB: 5T88
Notes: Mutagenesis of the ArM by error-prone PCR

Metal: Rh
Ligand type: OAc
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: N-H Insertion
Max TON: 73
ee: 40
PDB: 5T88
Notes: Mutagenesis of the ArM by error-prone PCR

Metal: Rh
Ligand type: OAc
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: S-H Insertion
Max TON: 64
ee: 32
PDB: 5T88
Notes: Mutagenesis of the ArM by error-prone PCR

Metal: Rh
Ligand type: OAc
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Reaction: Si-H Insertion
Max TON: 35
ee: 64
PDB: 5T88
Notes: Mutagenesis of the ArM by error-prone PCR

Manganese Terpyridine Artificial Metalloenzymes for Benzylic Oxygenation and Olefin Epoxidation

Lewis, J. C.

Tetrahedron, 2014, 10.1016/j.tet.2014.03.008


Metal: Mn
Ligand type: Poly-pyridine
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Max TON: 19.2
ee: ---
PDB: 3EMM
Notes: ---

Metal: Mn
Ligand type: Poly-pyridine
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Epoxidation
Max TON: 19.8
ee: ---
PDB: 3EMM
Notes: ---

Metallopeptide Catalysts and Artificial Metalloenzymes Containing Unnatural Amino Acids

Review

Lewis, J. C.

Curr. Opin. Chem. Biol., 2015, 10.1016/j.cbpa.2014.12.016


Notes: ---

Selective C–H Bond Functionalization Using Repurposed or Artificial Metalloenzymes

Review

Lewis, J. C.

Curr. Opin. Chem. Biol., 2017, 10.1016/j.cbpa.2016.12.027


Notes: ---