Gras, E.; Hureau, C.

Coord. Chem. Rev. 2016, 308, 445-459, 10.1016/j.ccr.2015.05.011

Artificial metalloenzymes, with their high selectivity and specificity combined with a wide scope of reactivity and substrates, constitute an original approach for catalyst development. Different strategies have been proposed for their elaboration, proceeding from modification of natural enzymes using bioengineering methods to de novo protein design. Another bio-inspired methodology for the development of hybrid catalysts consists in the incorporation of coordination complexes into biomolecules, with the aim to upgrade their catalytic abilities. In these systems, the reaction performed by the naked catalyst is modulated by the well-defined structure of the host biomolecule. This conveys added value to the catalyst, such as enantioselectivity or chemoselectivity. DNA, apo-enzymes, proteins and peptides have been engaged in this approach, affording a wide diversity of reactivities and substrates. The resulting systems can then be improved by combined chemical and bioengineering optimization, allowing access to powerful catalysts. Because this approach can virtually be applied to any biomolecule or coordination complex, the elaboration of bio-based hybrid catalysts seems promising for advance in catalysis.

Hilvert, D.; Jiménez-Osés, G.

Nat. Chem. 2021, 13, 231-235, 10.1038/s41557-020-00628-4

New enzyme catalysts are usually engineered by repurposing the active sites of natural proteins. Here we show that design and directed evolution can be used to transform a non-natural, functionally naive zinc-binding protein into a highly active catalyst for an abiological hetero-Diels–Alder reaction. The artificial metalloenzyme achieves >104 turnovers per active site, exerts absolute control over reaction pathway and product stereochemistry, and displays a catalytic proficiency (1/KTS = 2.9 × 1010 M−1) that exceeds all previously characterized Diels–Alderases. These properties capitalize on effective Lewis acid catalysis, a chemical strategy for accelerating Diels–Alder reactions common in the laboratory but so far unknown in nature. Extension of this approach to other metal ions and other de novo scaffolds may propel the design field in exciting new directions.

Mascareñas, J.L.

Angew. Chem. Int. Ed. 2020, 59, 9149-9154, 10.1002/anie.202002032

The generation of catalytically active metalloproteins inside living mammalian cells is a major research challenge at the interface between catalysis and cell biology. Herein we demonstrate that basic domains of bZIP transcription factors, mutated to include two histidine residues at i and i+4 positions, react with palladium(II) sources to generate catalytically active, stapled pallado-miniproteins. The resulting constrained peptides are efficiently internalized into living mammalian cells, where they perform palladium-promoted depropargylation reactions without cellular fixation. Control experiments confirm the requirement of the peptide scaffolding and the palladium staple for attaining the intracellular reactivity.

Bren, K.L.

Inorg. Chem. 2016, 55, 467-477, 10.1021/acs.inorgchem.5b02054

There has been great interest in the development of stable, inexpensive, efficient catalysts capable of reducing aqueous protons to hydrogen (H2), an alternative to fossil fuels. While synthetic H2 evolution catalysts have been in development for decades, recently there has been great progress in engineering biomolecular catalysts and assemblies of synthetic catalysts and biomolecules. In this Forum Article, progress in engineering proteins to catalyze H2 evolution from water is discussed. The artificial enzymes described include assemblies of synthetic catalysts and photosynthetic proteins, proteins with cofactors replaced with synthetic catalysts, and derivatives of electron-transfer proteins. In addition, a new catalyst consisting of a thermophilic cobalt-substituted cytochrome c is reported. As an electrocatalyst, the cobalt cytochrome shows nearly quantitative Faradaic efficiency and excellent longevity with a turnover number of >270000.