Marchetti, M.

Tetrahedron Lett. 2000, 41, 3717-3720, 10.1016/S0040-4039(00)00473-1

A highly efficient and chemoselective biphasic hydroformylation of olefins was accomplished using water soluble complexes formed by the interaction between Rh(CO)2(acac) and human serum albumin (HSA), a readily available water soluble protein. A new type of shape-selectivity was observed in the hydroformylation of sterically hindered olefins.

Klein Gebbink, R.J.M.; van Koten, G.

Tetrahedron Lett. 2011, 52, 1601-1604, 10.1016/j.tetlet.2011.01.106

The preparation of a heterogeneous bifunctional catalytic system, combining the catalytic properties of an organometallic catalyst (racemization) with those of an enzyme (enantioselective acylation) is described. A novel ruthenium phosphonate inhibitor was synthesized and covalently anchored to a lipase immobilized on a solid support (CALB, Novozym® 435). The immobilized bifunctional catalytic system showed activity in both racemization of (S)-1-phenylethanol and selective acylation of 1-phenylethanol.

Zeymer, C.

Protein Eng. Des. Sel. 2021, 34, 10.1093/protein/gzab003

Metalloproteins are essential to sustain life. Natural evolution optimized them for intricate structural, regulatory and catalytic functions that cannot be fulfilled by either a protein or a metal ion alone. In order to understand this synergy and the complex design principles behind the natural systems, simpler mimics were engineered from the bottom up by installing de novo metal sites in either natural or fully designed, artificial protein scaffolds. This review focuses on key challenges associated with this approach. We discuss how proteins can be equipped with binding sites that provide an optimal coordination environment for a metal cofactor of choice, which can be a single metal ion or a complex multinuclear cluster. Furthermore, we highlight recent studies in which artificial metalloproteins were engineered towards new functions, including electron transfer and catalysis. In this context, the powerful combination of de novo protein design and directed evolution is emphasized for metalloenzyme development.

Arnold, F.H.; Fasan, R.

Curr. Opin. Biotechnol. 2017, 47, 102-111, 10.1016/j.copbio.2017.06.005

The surge in reports of heme-dependent proteins as catalysts for abiotic, synthetically valuable carbene and nitrene transfer reactions dramatically illustrates the evolvability of the protein world and our nascent ability to exploit that for new enzyme chemistry. We highlight the latest additions to the hemoprotein-catalyzed reaction repertoire (including carbene Si–H and C–H insertions, Doyle–Kirmse reactions, aldehyde olefinations, azide-to-aldehyde conversions, and intermolecular nitrene C–H insertion) and show how different hemoprotein scaffolds offer varied reactivity and selectivity. Preparative-scale syntheses of pharmaceutically relevant compounds accomplished with these new catalysts are beginning to demonstrate their biotechnological relevance. Insights into the determinants of enzyme lifetime and product yield are providing generalizable cues for engineering heme-dependent proteins to further broaden the scope and utility of these non-natural activities.

Ward, T.R.

Curr. Opin. Biotechnol. 2010, 21, 744-752, 10.1016/j.copbio.2010.09.004

Artificial metalloenzymes result from the introduction of a catalytically competent non-native metal cofactor within a protein environment. In the present contribution, we summarize the recent achievements in the design and the optimization of such protein-based hybrid catalysts, with an emphasis on enantioselective transformations. The second part outlines the milestones required to achieve en masse production, screening and directed evolution of artificial metalloenzymes. In the spirit of Darwinian evolution, this will allow the full potential of such protein-based hybrid catalysts to be fully unraveled, thus complementing both homogeneous and enzymatic catalysis.

Matsuo, T.

Tetrahedron Lett. 2019, 60, 151226, 10.1016/j.tetlet.2019.151226

Organic synthesis using biocatalysts has been developed over many years and is still a prominent area of research. In this context, various hybrid biocatalysts composed of a synthetic metal complex catalyst and a protein scaffold (i.e. artificial metalloenzymes) have been constructed. One of the most recent research areas in biocatalysts-mediated synthesis is CC bond/cleavage, the most important type of reaction in organic chemistry. Some of the artificial enzymes were applied to in-cell reactions as well as in vitro systems. The effects of the structural fluctuation in biomacromolecules on their functions have also been realized. This review article includes recent research examples of artificial metalloenzymes used to CC bond formation/cleavage. As a perspective, we also focus on how we apply protein dynamics factor for the creation of new generation artificial metalloenzymes.

Mahy, J.-P.

Tetrahedron Lett. 2008, 49, 1865-1869, 10.1016/j.tetlet.2008.01.022

The synthesis of a new cationic iron metalloporphyrin–estradiol conjugate is reported. After a study of its association with the anti-estradiol antibody 7A3 by UV–visible spectroscopy, the influence of the antibody on the sulfoxidation of thioanisole by H2O2 catalyzed by the iron–metalloporphyrin has been investigated.