3 publications

3 publications

An Artificial Hemoprotein with Inducible Peroxidase‐ and Monooxygenase‐Like Activities

Ricoux, R.

Chem. Eur. J. 2020, 26, 14929-14937, 10.1002/chem.202002434

A novel inducible artificial metalloenzyme obtained by covalent attachment of a manganese(III)-tetraphenylporphyrin (MnTPP) to the artificial bidomain repeat protein, (A3A3′)Y26C, is reported. The protein is part of the αRep family. The biohybrid was fully characterized by MALDI-ToF mass spectrometry, circular dichroism and UV/Vis spectroscopies. The peroxidase and monooxygenase activities were evaluated on the original and modified scaffolds including those that have a) an additional imidazole, b) a specific αRep bA3-2 that is known to induce the opening of the (A3A3′) interdomain region and c) a derivative of the αRep bA3-2 inducer extended with a His6-Tag (His6-bA3-2). Catalytic profiles are highly dependent on the presence of co-catalysts with the best activity obtained with His6-bA3-2. The entire mechanism was rationalized by an integrative molecular modeling study that includes protein–ligand docking and large-scale molecular dynamics. This constitutes the first example of an entirely artificial metalloenzyme with inducible peroxidase and monooxygenase activities, reminiscent of allosteric regulation of natural enzymatic pathways.

Metal: Mn
Ligand type: Porphyrin
Anchoring strategy: Covalent
Optimization: ---
Reaction: Peroxidation
Max TON: ---
ee: ---
PDB: ---
Notes: ---

DNA‐Based Asymmetric Inverse Electron‐Demand Hetero‐Diels–Alder

Arseniyadis, S.; Campagne, J.; Smietana, M.

Chem. Eur. J. 2020, 26, 3519-3523, 10.1002/chem.202000516

While artificial cyclases hold great promise in chemical synthesis, this work presents the first example of a DNA-catalyzed inverse electron-demand hetero-Diels–Alder (IEDHDA) between dihydrofuran and various α,β-unsaturated acyl imidazoles. The resulting fused bicyclic O,O-acetals containing three contiguous stereogenic centers are obtained in high yields (up to 99 %) and excellent diastereo- (up to >99:1 dr) and enantioselectivities (up to 95 % ee) using a low catalyst loading. Most importantly, these results show that the concept of DNA-based asymmetric catalysis can be expanded to new synthetic transformations offering an efficient, sustainable, and highly selective tool for the construction of chiral building blocks.

Metal: Cu
Ligand type: Cu(dmbipy)(NO3)2
Host protein: DNA
Anchoring strategy: Supramolecular
Optimization: Chemical
Max TON: 3.33
ee: 95
PDB: ---
Notes: ---

Enhanced Photocatalytic Hydrogen Production by Hybrid Streptavidin‐Diiron Catalysts

Chem. Eur. J. 2020, 26, 6240-6246, 10.1002/chem.202000204

Hybrid protein–organometallic catalysts are being explored for selective catalysis of a number of reactions, because they utilize the complementary strengths of proteins and of organometallic complex. Herein, we present an artificial hydrogenase, StrepH2, built by incorporating a biotinylated [Fe–Fe] hydrogenase organometallic mimic within streptavidin. This strategy takes advantage of the remarkable strength and specificity of biotin-streptavidin recognition, which drives quantitative incorporation of the biotinylated diironhexacarbonyl center into streptavidin, as confirmed by UV/Vis spectroscopy and X-ray crystallography. FTIR spectra of StrepH2 show characteristic peaks at shift values indicative of interactions between the catalyst and the protein scaffold. StrepH2 catalyzes proton reduction to hydrogen in aqueous media during photo- and electrocatalysis. Under photocatalytic conditions, the protein-embedded catalyst shows enhanced efficiency and prolonged activity compared to the isolated catalyst. Transient absorption spectroscopy data suggest a mechanism for the observed increase in activity underpinned by an observed longer lifetime for the catalytic species FeIFe0 when incorporated within streptavidin compared to the biotinylated catalyst in solution.

Metal: Fe
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: ---
Reaction: H2 evolution
Max TON: 47.63 (± 3.16)
ee: ---
Notes: Photocatalytic activity, expressed as TON, for ArM is about 8 times higher than that of the biotinylated cofactor.The increase in TON is largely due to increased lifetime of the catalytically competent intermediate, FeIFe0 core when embeded inside streptavidin.