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Non-covalent interactions are very diverse, and they are generally difficult to investigate through experimental methods. Here tailored metal–organic frameworks serve as a platform for the systematic generation of a variety of non-covalent interactions, which can be studied through the electric fields produced by the charges and dipoles involved in the interactions.

Directed evolution of the final enzyme in the lovastatin biosynthetic pathway yields a variant with 29 mutations that does not require a carrier protein and displays altered dynamics of the catalytic residues, spending more time in the catalytically active conformation.

By enriching productive mutational paths, a Kemp eliminase that speeds up proton abstraction >10⁸-fold was developed in only five evolution rounds. Recombining it with a variant differing by 29 substitutions revealed the underlying fitness landscape.

A strategy for protecting redox-active ortho-quinones, which show promise as anticancer agents but suffer from redox-cycling behaviour and systemic toxicity, has been developed. The ortho-quinones are derivatized to redox-inactive para-aminobenzyl ketols. Upon amine deprotection, an acid-promoted, self-immolative C–C bond-cleaving 1,6-elimination releases the redox-active hydroquinone. The strategy also enables conjugation to a carrier for targeted delivery of ortho-quinone species.

To study neurodegenerative prion diseases, a method (PMSA) for generating prions spontaneously is presented. Applied to 380+ different prion proteins, their tendency to become pathogenic was ranked, illuminating their formation process.

Stabilization of gold nanoclusters in order to prevent their self-aggregation remains a great challenge. Here, the authors describe transient stabilization of very small catalytic gold subnanoclusters by alkyl chains or aromatic groups appended to the reactive π bond of simple alkynes.

Anthocyanins are used in the food and cosmetic industries. Due to the insufficient production in alternative hosts, they are still isolated from plants. Now, this study suggests an important catalytic role of glutathione transferases for the efficient biosynthesis of these natural products.

Current cysteine bioconjugation strategies for protein-drug conjugates synthesis often yield heterogeneous and poorly stable products. Here, the authors use carbonylacrylic derivatives to selectively modify cysteine residues and synthesize biologically functional antibody conjugates highly stable in plasma.

A de novo designed zinc-binding protein has been converted into a highly active, stereoselective catalyst for a hetero-Diels–Alder reaction. Design and directed evolution were used to effectively harness Lewis acid catalysis and create an enzyme more proficient than other reported Diels–Alderases.

During the biosynthesis of the lanthipeptide duramycin, DurN catalyzes stereospecific lysinoalanine formation by preorganizing the reactive conformation of the substrate, such that one of the substrate’s own residues serves as the catalytic base.

The reactivity of a monooxygenase (P450 PikC) has been modified through protein and substrate engineering, and applied to the oxidation of unactivated methylene C–H bonds. The protein engineering was guided by using molecular dynamics and quantum mechanical calculations to develop a predictive model for substrate scope, site selectivity and stereoselectivity of the C–H hydroxylation.

The stereochemical outcome of enzyme-catalysed reactions with physiological substrates is typically governed by the well-defined geometry of the enzyme active site. Now, a rare example is reported where the substrate controls the stereoselectivity of a Michael-type addition during lanthipeptide biosynthesis.

A structural and functional study including a mutational analysis of C. elegans POFUT2 with GDP and a peptide substrate helps explain how this and other fucosyltransferases recognize protein substrates with diverse sequences.

GalNAc transferases’ (GalNAc-Ts) catalytic domains are connected to a lectin domain through a flexible linker. Here the authors present a structural analysis of GalNAc-T4 that implicates the linker region as modulator of the orientations of the lectin domain, which in turn imparts substrate specificity.

Site-selective modification of antibodies is useful for therapeutic and imaging applications. This protocol is an alternative to maleimide labeling in which cysteine reacts selectively and irreversibly with functionalized carbonylacrylic reagents.