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Enzyme catalysis is essential for molecular transformations. Here, the authors show that incorporation of an amyloid recognition motif (azo-stilbene derivative) into the substrate allows the amyloid consisting of Bz-Phe-Phe-Ala-Ala-Leu-Leu-NH2 to shield the substrate from the approaching enzyme.

Sulfoquinovosyl diacylglycerols are produced by photosynthetic organisms and serve as sources of carbon and sulfur for bacteria. This work characterizes a sulfoquinovosidase, unveils a reservoir of organosulfur compounds in the ocean and elucidates their critical role in marine carbon cycling.

The first high-resolution structures of transaldolase with bound intermediates both define active site residues that necessitate a revision of the current reaction pathway and point to a high-energy intermediate structure and protein conformational changes as mechanisms to promote product formation.

Researchers identified a subclass of lanthionine synthetase KC enzymes, revealing a functional dimer captured in different peptide binding states with a salt bridge required for catalysis.

Structural and biochemical analysis of E. coli transketolase with 2′-methoxy-thiamine shows that this antivitamin selectively inhibits the bacterial enzyme via a steric clash with a critical glutamate residue, preventing cofactor activation.

The S-methyltransferase enzyme MddH produces DMS from hydrogen sulfide and methanethiol and its gene abundance rivals that of other known genes whose products generate DMS in marine environments.

The natural hallucinogen psilocybin — produced by so-called magic mushrooms — holds promise for the treatment of depression and other mental health conditions. Here, the authors provide a structural and biochemical analysis of the Psilocybe methyl transferase PsiM that provides mechanistic insight into the last step of psilocybin biosynthesis.

The recovery of North American forests is likely to impact their capacity as a carbon sink. Here, Zhu et al. show a growth in aboveground biomass in various climate change scenarios, with these forests expected to sequester no more than 22% more carbon than current levels by the 2080s.

Simple enzyme mimetics are highly desired for industrial settings providing high catalyst stability and low production costs. This work reports that phenylalanine and zinc ions can self-assemble into a supramolecular structure showing catalytic properties similar to those of the natural enzyme carbonic anhydrase.

Quorum sensing is a regulatory mechanism controlling bacterial signaling and ComA, a conserved efflux pump, is responsible for the maturation and secretion of peptide signals. Here, authors determine the 3D structure and demonstrate its function as an ABC transporter.

Maintenance of NADPH levels during environmental stress can prolong cell survival. Ding et al. identify MESH1 as a cytosolic NADPH phosphatase that is required for the metabolic commitment to ferroptosis in cancer cell lines.

Asymmetric reduction of prochiral ketones is challenging. Here, the authors identify and solve the structure of anthrol reductase CbAR, whose variant H162F can convert 1,3-cyclodiketones and α-haloacetophenones to the corresponding chiral alcohols.

A NOS bridge between cysteine and lysine residues serves as an allosteric redox switch in the transaldolase enzyme of Neisseria gonorrhoeae, demonstrating the existence of protein regulatory switches that contain covalent crosslinks other than disulfides.

The complete biosynthetic pathway of Prim-O-Glucosylcimifugin and 5-O-Methylvisamminoside in Saposhnikovia divaricata is resolved and their de novo biosynthesis is reconstructed in Nicotiana benthamiana leaves. The evolutionary mechanisms of furochromone biosynthesis among Apiaceae plants is further analyzed.

Cryo-electron microscopy and biochemical analysis reveal the activation mechanism of protein arginine kinase McsB by its activator McsA for protein quality control under stress in Gram-positive bacteria.

Carbenes have been postulated to take part in the catalytic cycle of several enzymes, but direct detection of these unstable compounds has been elusive. Spectroscopic and structural studies of pyruvate oxidase now identify a carbene-containing cofactor, calling for reinspection of existing enzyme mechanisms.

Rescue of ribosomes stalled on non-stop mRNA is essential for cell viability, and several rescue systems to resolve stalling exist in bacteria. Here, the authors use rapid kinetics and cryo-EM to reveal the pathway and selectivity mechanism of ArfB-mediated ribosome rescue.

Ground state destabilization is often evoked as a possible explanation of orotidine-5′-phosphate decarboxylase catalysis. Now, high-resolution structures of this enzyme provide time-resolved snapshots along its reaction coordinate revealing that transition-state stabilization by electrostatic interactions drives its reactivity.

A survey of protein structures identifies widespread lysine–cysteine cross-links in functionally diverse proteins across all domains of life and in various structural motifs, where these redox switches control enzyme catalysis and/or ligand binding.

Sonodynamic therapy is an emerging non-invasive antitumor strategy, but its efficiency is limited by the rapid electron and hole recombination of traditional semiconductor sonosensitizers under ultrasonic stimulation. Here, the authors address this issue by developing a Zn/Pt dual-site single-atom driven difunctional superimposition-augmented TiO₂-based sonosensitizer.

SLC25A51 is identified as a transporter of intact NAD⁺ into mammalian mitochondria and is required to maintain the mitochondrial NAD⁺ pool and respiratory function.

Nicotine accumulates in the intestine during tobacco smoking and accelerates the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), but it can be degraded effectively by the human symbiont Bacteroides xylanisolvens.

Genetic engineering of yeast enables the production of cannabinoids and cannabinoid analogues from the simple sugar galactose, without the need to cultivate Cannabis.

Structural and biophysical studies reveal that low-barrier hydrogen bonds enable long-range communication between the active sites of multimeric enzymes and synchronise catalysis.

The hetero-Diels–Alder reaction is a powerful strategy for constructing six-membered heterocycles, yet natural enzymatic hetero-Diels–Alder reactions are limited to a single heteroatom. Now a bifunctional enzyme, Abx₍₋₎F, is found to catalyse the dehydration and a dual-oxa Diels–Alder reaction to form the oxygen-bridged tricyclic acetal of (−)-anthrabenzoxocinones.

HLA-DM activity ensures that only high-affinity peptides are displayed on MHC class II molecules. Wucherpfennig and colleagues show that interaction of HLA-DR with the N terminus of bound peptides determines susceptibility to HLA-DM.

M. tuberculosis NAD⁺ synthetase (tbNadE) is of interest as a drug target. Here the authors present the actively trapped Homo sapiens NAD⁺ synthetase (hsNadE) and tbNadE structures and show key differences in the synthetase active site and in structural elements possibly involved in the allosteric regulation of catalysis to be leveraged for the development of M. tuberculosis selective inhibitors.

NADP can directly bind with FTO and enhance its m⁶A demethylase activity, thus affecting RNA m⁶A modification and adipogenesis.

The northern temperate carbon sink is estimated to increase by 0.64 PgC each year for each increase in atmospheric CO₂ concentrations by 100 ppm, suggests an analysis of data from field experiments at 7 sites constraints.

Continuous low-level supply or in situ generation of hydrogen peroxide (H₂O₂) is essential for the stability of unspecific peroxygenases. Here, the authors demonstrate that AuPd / TiO₂ can generate sufficient H₂O₂ for the engineered unspecific heme-thiolate peroxygenase PaDa-I to oxidise a range of C-H bonds.

Single-cell transcriptomics reveals that, in mice and humans, a population of cells in the stromal vascular fraction of adipose tissue regulates adipogenesis by suppressing adipocyte formation in a paracrine manner.

Proton pumping of mitochondrial complex I depends on the reduction of ubiquinone but the molecular mechanism of energy conversion is unclear. Here, the authors provide structural and biochemical evidence showing that movement of loop TMH1-2 in complex I subunit ND3 is required to drive proton pumping.

Marine cyanobacteria contribute to global carbon balance by fixing CO₂ and the shift between CO₂ fixation and ATP production requires fine-tuning its metabolic fluxes to light–dark cycles. These cycles can be very short in marine environments due to sea currents and fast adaptation is key to avoid futile cycles. In this study, Lu et al. provide a mechanistic insight into how this process is tightly regulated.

Mitophagy activation is mediated by mitochondrial depolarization. Here, the authors show that mitochondrial protein misfolding can activate mitophagy in a depolarization-independent manner mediated by a protein import reduction.

Rothenburger et al. combine the analysis of data from large pharmacogenomics screens with cell line experiments to elucidate mechanisms behind nelarabine resistance in acute lymphoblastic leukaemia (ALL). They identify low expression of the dNTP hydrolase SAMHD1 as a determinant of nelarabine sensitivity, suggesting the enzyme as a biomarker.