Abstract
Artificial metalloenzymes (ArMs) result from the incorporation of an abiotic metal cofactor within a protein scaffold. From the earliest techniques of transition metals adsorbed on silk fibers, the field of ArMs has expanded dramatically over the past 60 years to encompass a range of reaction classes and inspired approaches: Assembly of the ArMs has taken multiple forms with both covalent and supramolecular anchoring strategies, while the scaffolds have been intuitively selected and evolved, repurposed, or designed in silico. Herein, we discuss some of the most prominent recent examples of ArMs to highlight the challenges and opportunities presented by the field.
Highlights
In 1956, Fujii and co-workers reported on the use of reduced palladium chloride adsorbed on silk fibers for the asymmetricScheme 1
A(a) Dative anchoring resulting from metal substitution in carboxypeptidase A (CPA). (b) Supramolecular anchoring based on the biotin-avidin technology. (c) Covalent anchoring to an engineered cysteine within adipocyte lipid binding protein (ALBP)
Reduction of dehydro-amino acid derivatives.[1]. These findings have proven challenging to reproduce, this contribution is generally considered to be the first report on a metal-catalyzed asymmetric reaction.[2]. This protein-modified precious metal catalyst satisfies the generic definition of an artificial metalloenzyme (ArM hereafter): a hybrid catalyst that results from combining an abiotic metal cofactor with a protein
Summary
In 1956, Fujii and co-workers reported on the use of reduced palladium chloride adsorbed on silk fibers for the asymmetric. Unnatural Amino Acids Bearing a Chelating Group (i.e., Biypridine-alanine BpyA) Allow the Anchoring of Copper into Homodimeric Lactococcal Multidrug Resistance Regulator (LmrR), and Site-Directed Mutagenesis of Second Coordination Sphere Residues Leads to a Significantly Improved Artificial Hydratase anchoring of Cu(II) to its host protein, Roelfes and co-workers engineered a bipyridine-alanine (BpyA) in the hydrophobic pocket of the lactococcal multidrug resistance regulator (LmrR) homodimeric scaffold.[41] Complementation with Cu(II) afforded an ArM (Cu·LmrR M89BpyA) that catalyzed the enantioselective hydration of prochiral enones. The natural cofactor of hemoproteins may be altered in three ways to achieve novel reactivity: modification of the scaffold, addition of functional groups, and/or substitution of the metal.[51] The first approach has been utilized by Hayashi and co-workers to assemble a myoglobin (Mb)-based ArM that catalyzes cyclopropanation.[52] Myoglobin was expressed, the heme removed and replaced with the iron porphycene 27, Scheme 16a.
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