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.

Ménage, S.

J. Mol. Catal. A: Chem. 2016, 416, 20-28, 10.1016/j.molcata.2016.02.015

A new artificial oxidase has been developed for selective transformation of thioanisole. The catalytic activity of an iron inorganic complex, FeLibu, embedded in a transport protein NikA has been investigated in aqueous media. High efficiency (up to 1367 t), frequency 459 TON min−1 and selectivity (up to 69%) make this easy to use catalytic system an asset for a sustainable chemistry.

Lee, S.-Y.

Chem. - Asian J. 2018, 13, 334-341, 10.1002/asia.201701543

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme with a Zn cofactor coordinated to trigonal histidine imidazole moieties in a tetrahedral geometry. Removal of the Zn cofactor in CA and subsequent binding of Ir afforded CA[Ir]. Under mild and neutral conditions (30 °C, pH 7), CA[Ir] exhibited water‐oxidizing activity with a turnover frequency (TOF) of 39.8 min−1, which is comparable to those of other Ir‐based molecular catalysts. Coordination of Ir to the apoprotein of CA is thermodynamically preferred and is associated with an exothermic energy change (ΔH) of −10.8 kcal mol−1, which implies that the CA apoprotein is stabilized by Ir binding. The catalytic oxygen‐evolving activity of CA[Ir] is displayed only if Ir is bound to CA, which functions as an effective biological scaffold that activates the Ir center for catalysis. The results of this study indicate that the histidine imidazoles at the CA active site could be exploited as beneficial biological ligands to provide unforeseen biochemical activity by coordination to a variety of transition‐metal ions.

Cavazza, C.; Ménage, S.

J. Am. Chem. Soc. 2017, 139, 17994-18002, 10.1021/jacs.7b09343

Designing systems that merge the advantages of heterogeneous catalysis, enzymology, and molecular catalysis represents the next major goal for sustainable chemistry. Cross-linked enzyme crystals display most of these essential assets (well-designed mesoporous support, protein selectivity, and molecular recognition of substrates). Nevertheless, a lack of reaction diversity, particularly in the field of oxidation, remains a constraint for their increased use in the field. Here, thanks to the design of cross-linked artificial nonheme iron oxygenase crystals, we filled this gap by developing biobased heterogeneous catalysts capable of oxidizing carbon–carbon double bonds. First, reductive O2 activation induces selective oxidative cleavage, revealing the indestructible character of the solid catalyst (at least 30 000 turnover numbers without any loss of activity). Second, the use of 2-electron oxidants allows selective and high-efficiency hydroxychlorination with thousands of turnover numbers. This new technology by far outperforms catalysis using the inorganic complexes alone, or even the artificial enzymes in solution. The combination of easy catalyst synthesis, the improvement of “omic” technologies, and automation of protein crystallization makes this strategy a real opportunity for the future of (bio)catalysis.

Ménage, S.

Artificial Metalloenzymes and MetalloDNAzymes in Catalysis: From Design to Applications 2018, 199-224, 10.1002/9783527804085.ch7

Artificial metalloenzymes broadens the scope of possibilities for catalysis at the crossroad of biocatalysis and metal‐based catalysis. The content of this chapter illustrates this outline in the field of oxidation, thanks to remarkable achievements for epoxidation and sulfoxidation in particular. Selectivity, especially enantioselectivity, is benchmarked based on six design strategies (ranging from protein engineering to de novo design), revealing that artificial systems may compete natural ones.

Ménage, S.

Isr. J. Chem. 2015, 55, 61-75, 10.1002/ijch.201400110

The principle of enzyme mimics has been raised to its pinnacle by the design of hybrids made from inorganic complexes embedded into biomolecules. The present review focuses on the design of artificial metalloenzymes for oxidation reactions by oxygen transfer reactions, with a special focus on proteins anchoring inorganic complexes or metal ions via supramolecular interactions. Such reactions are of great interest for the organic synthesis of building blocks. In the first part, following an overview of the different design of artificial enzymes, the review presents contributions to the rational design of efficient hybrid biocatalysts via supramolecular host/guest approaches, based on the nature of the inorganic complex and the nature of the protein, with special attention to the substrate binding. In the second part, the original purpose of artificial metalloenzymes has been twisted to enable the observation of transient intermediates, to decipher metal‐based oxidation mechanisms. The host protein crystals have been used as crystalline molecular‐scale vessels, within which inorganic catalytic reactions have been followed, thanks to X‐ray crystallography. These hybrids should be an alternative to enzymes for sustainable chemistry.

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.