LongLarf

The catalytic repertoire of nature has been expanded over the past decades by the introduction of artificial metalloenzymes. These are enzymes containing a synthetic metal complex or a non-native metal ion. However, combining noble metal catalysis and enzymes remains challenging due to the lack of suitable ligands to bind these complexes. So far, noble metal artificial metalloenzyme design mostly involves in vitro approaches of ligand anchoring, like covalent modification of a cysteine residue or via supramolecular assembly. Here, we show a facile strategy to anchor a variety of 4d and 5d-transition metal complexes via genetic incorporation of a thiophenolic metal-binding ligand. We created a methodology to efficiently incorporate 4-mercaptophenylalanine in a protein scaffold using the stop codon suppression technology. The incorporated non-canonical amino acid was capable of binding a variety of noble metal complexes. To showcase the catalytic applications of this methodology, we developed an artificial hydroaminase by binding gold ions to the thiophenol-containing protein. The benefit of in vivo incorporation of the ligand is demonstrated by the susceptibility of catalytic activity to the microenvironment around the metal site, which can be modulated by changing the position of the ligand within the protein or by mutation of residues in its proximity.

The Cover Feature illustrates that in a hybrid catalysis process, it is possible to harness the essential qualities of both the biocatalyst and the chemical catalyst, enabling them to contribute equally to the reaction performance, even under typically unfavorable conditions of pH, temperature, and solvent. Specifically, in their Concept article, Christine Guérard-Hélaine and co-workers have chosen publications that report only the rare one-pot processes operating in concurrent mode, where all the reaction ingredients are added from the beginning. The authors demonstrate how it is possible to resolve incompatibility issues between catalysts, forced to work together in synergy under common experimental conditions. More information can be found in the Concept by C. Guérard-Hélaine and co-workers (DOI: 10.1002/cctc.202301703).

Highly stereoselective Michael addition of cyclic ketones to nitroolefins was promoted by a designer artificial enzyme harboring a catalytic pyrrolidine residue through enamine catalysis. Diverse chiral γ-nitroketones were prepared by this efficient biocatalytic strategy for ketone functionalization in a study highlighting the utility of artificial enzymes for new-to-nature reactions.

Abstract

Consistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new-to-nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ-nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97 % e.e., >20 : 1 d.r.) and good yield (up to 86 %). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization, and highlights the usefulness of artificial enzymes for extending biocatalysis to further non-natural reactions.

Nature Catalysis, Published online: 29 May 2024; doi:10.1038/s41929-024-01176-7

A boronic enzyme

Nature, Published online: 08 May 2024; doi:10.1038/s41586-024-07391-3

A completely genetically encoded boronic-acid-containing designer enzyme was created and characterized using X-ray crystallography, high-resolution mass spectrometry and 11B NMR spectroscopy, allowing chemistry that is unknown in nature and currently not possible with small-molecule catalysts.

Nature, Published online: 01 May 2024; doi:10.1038/s41586-024-07284-5

We report on the oxidative cross-coupling of organoboron reagents and amino acids via pyridoxal biocatalysis to produce non-canonical amino acids, uncovering stereoselective, intermolecular free-radical transformations.

Nature Chemistry, Published online: 17 April 2024; doi:10.1038/s41557-024-01494-0

Despite their intriguing photochemical activities, natural photoenzymes have not yet been repurposed for new-to-nature activities. Now, by leveraging the strongly oxidizing excited-state flavoquinone cofactor, fatty acid photodecarboxylases were engineered to catalyse unnatural decarboxylative radical cyclization with excellent chemo-, enantio- and diastereoselectivities.