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Controlled Ligand Exchange Between Ruthenium Organometallic Cofactor Precursors and a Naïve Protein Scaffold Generates Artificial Metalloenzymes Catalysing Transfer Hydrogenation.

Accepted version
Peer-reviewed

Type

Article

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Abstract

Many natural metalloenzymes assemble from proteins and biosynthesised complexes, generating potent catalysts by changing metal coordination. Here we adopt the same strategy to generate artificial metalloenzymes (ArMs) using ligand exchange to unmask catalytic activity. By systematically testing RuII (η6 -arene)(bipyridine) complexes designed to facilitate the displacement of functionalised bipyridines, we develop a fast and robust procedure for generating new enzymes via ligand exchange in a protein that has not evolved to bind such a complex. The resulting metal cofactors form peptidic coordination bonds but also retain a non-biological ligand. Tandem mass spectrometry and 19 F NMR spectroscopy were used to characterise the organometallic cofactors and identify the protein-derived ligands. By introduction of ruthenium cofactors into a 4-helical bundle, transfer hydrogenation catalysts were generated that displayed a 35-fold rate increase when compared to the respective small molecule reaction in solution.

Description

Keywords

direct coordination, ligand exchange, metalloenzymes, ruthenium, transfer hydrogenation, Catalysis, Fluorine, Hydrogenation, Ligands, Magnetic Resonance Spectroscopy, Metalloproteins, Molecular Structure, Organometallic Compounds, Ruthenium

Journal Title

Angew Chem Int Ed Engl

Conference Name

Journal ISSN

1433-7851
1521-3773

Volume Title

60

Publisher

Wiley

Rights

All rights reserved
Sponsorship
European Commission Horizon 2020 (H2020) ERC (695664)
Engineering and Physical Sciences Research Council (EP/N509620/1)
Engineering and Physical Sciences Research Council (1800459)