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The preparation of functionalized amino acids from inexpensive aldehydes is challenging. This work describes the biocatalytic synthesis of l-methionine by applying gaseous CO₂ pressure and a coupled amination step to drive the unfavoured equilibrium of a reverse carboxylation reaction.

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.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

Renilla luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Now, protein crystal structures and biochemical analyses provide an atomistic description of its catalytic mechanism.

For many enzymes, it is unknown which primary and/or secondary reactions they catalyze. Here, the authors use machine and deep learning to develop a general model for the prediction of enzyme-small molecule substrate pairs and make the resulting model available through a webserver.

The oomycete Phytophthora infestans is a damaging crop pathogen. Here, the authors show that a group of P. infestans secreted enzymes play roles in penetration and colonization of host plants by oxidising fragments of the polysaccharide pectin in the plant cell wall.

The protein translation machinery is the most expensive cellular subsystem in fast growing bacteria. Providing a detailed mechanistic model for this complex system, the authors show that the translation machinery components are expressed such that their combined cost to the cell is minimal.

The turnover numbers of most enzyme-catalyzed reactions are unknown. Kroll et al. developed a general model that can predict turnover numbers even for enzymes dissimilar to those used for training, outperforming existing models.

Active fluids that consume local fuels to generate movements can be utilized to promote mixing in microfluidic devices. Here, Bate et al. show a transition from diffusion-like to superdiffusion-like behaviours with mixing efficacy depending on the Péclet number and spatial distribution of activities.

The sugar d-apiose is important in plant cell wall polysaccharides. Here the authors elucidate the complex, multistep biosynthetic pathway for its production using enzyme crystal structures and computational analysis.

NanoLuc luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Here the authors use, protein crystal structures and biochemical analyses to provide an atomistic description of its catalytic mechanism and allosteric behaviour.

Sequence-specific binding of PCBP1 to poly-cytosine DNA enhances cGAS-STING activation and interferon-driven immune responses, revealing a new co-sensing mechanism that restrains breast tumor growth.

Friedrich Luft and colleagues identify missense mutations in PDE3A in six unrelated families with an autosomal dominant syndrome marked by severe hypertension and brachydactyly. They further show that the mutations result in gain of enzymatic function, leading to increased vascular smooth muscle cell proliferation and vessel wall hyperplasia.

The development of innovative strategies for the capture and biodegradation of nanoplastics is sought after. Now, artificial hydrolytic active sites are incorporated into non-catalytic membrane nanopores generating pore-based biocatalytic nanoreactors that depolymerize polyethylene terephthalate plastic nanoparticles.

Ruminococcus gnavus is a mucus-associated gut commensal that can release the sialic acid, 2,7-anhydro-Neu5Ac. Here, the authors identify the pathway for its transportation and metabolism in R. gnavus, and show that this pathway is essential for its spatial localization in vivo.

Here, Arkinson et al. reconstitute NUB1-mediated FAT10 degradation by the human 26S proteasome and use biochemistry, cryo-EM and hydrogen–deuterium exchange to show that NUB1 acts as an ATP-independent chaperone to trap partially folded FAT10 for proteasome delivery.

Radical Fe^II/α-ketoglutarate-dependent halogenases are powerful biocatalysts for C–H functionalization. Here, the authors reveal the mechanistic basis for chemoselectivity in a lysine halogenase.

Photoreceptor proteins utilise biological chromophores to regulate a large range of cellular processes in response to light. Here the authors identify and characterise a sub-family of multi-centre photoreceptors, termed photocobilins, that not only utilise B₁₂ but also contain biliverdin (BV) as an additional chromophore.

Genome-scale models of microbial metabolism largely ignore reaction kinetics. Here, the authors develop a general mathematical framework for modeling cellular growth with explicit non-linear reaction kinetics and use it to glean insights into the principles of cellular resource allocation and growth.

The bacterial insertase BAM is a key target for novel antibiotics that are urgently needed. Here, we describe the implementation of an assay that allows screening for BAM inhibitors in the native membrane in high-throughput format.

The bacterial AAA+ ClpX unfolds substrates using the energy from ATP hydrolysis and delivers them to the associated protease ClpP. A loop with an aromatic-hydrophobic motif protrudes into the central pore of the ClpX hexamer and was known to be important for activity. Now mutational analysis using covalently linked subunits provides evidence that this loop actually grips the substrate and undergoes conformational changes to drive its translocation and unfolding.

Rare mutations in the high requirement temperature protein A1 (HTRA1) cause cerebral vasculopathy. Here, authors establish mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the assembly and protease function of HTRA1.

Protein kinase transition between different conformational states is controlled by autophosphorylation. Here, the authors demonstrate that the c-terminal Tyr530 is a de facto c-Src autophosphorylation site  and identify a critical c-terminal palindromic phospho-motif that controls the interplay between substrate and enzyme-acting kinases during autophosphorylation.

Rpn11, the only essential deubiquitinase (DUB) of the 26S proteasome, sits at the top of the substrate entry pathway and facilitates substrate degradation through cotranslocational deubiquitination. The structure of the Rpn11–Rpn8 complex, together with functional assays, offers insight into Rpn11's promiscuous DUB activity during proteasomal degradation.

RNA repair helps bacteria survive antibiotic stress. Here, authors show that Rtc-driven repair causes cell-to-cell variation in resistance levels, revealing a potential form of heteroresistance, and identify key Rtc targets to enhance antibiotic effectiveness.

Adenylate cyclase activity in TIR1/AFB, the canonical auxin receptor, has an essential role in auxin-mediated root growth inhibition in land plants.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Characterization of xylan utilization loci in the butyrate-producing Firmicute Roseburia intestinalis provides mechanistic insight into its growth on different xylan substrates and its ability to co-grow and compete with a xylan-degrading commensal from the Bacteroides genus.

Directed evolution commonly relies on point mutations but InDels frequently occur in evolution. Here the authors report a protein-engineering framework based on InDel mutagenesis and fragment transplantation resulting in greater catalysis and longer glow-type bioluminescence of the ancestral luciferase.

In C₄ grasses, malate is decarboxylated by NADP-malic enzyme in bundle sheath cells. The structures of maize and sorghum varieties identify amino acids important for catalytic efficiency, tetrameric structure and pH-dependent inhibition malate

Scholze et al. investigate individual UV exposure and 25(OH)D₃ metabolism in a one-year observational study. While UV exposure triggers vitamin D₃ production, the body strongly modulates the resulting 25(OH)D₃ concentrations through 25(OH)D₃ synthesis efficiency and degradation, with the seasonal pattern mirroring local temperature fluctuations.

Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediates multidrug resistance, but its natural function remains unclear. Here, Shafik et al. show that PfCRT transports host-derived peptides of 4-11 residues but not other ions or metabolites, and that drug-resistance-conferring PfCRT mutants have reduced peptide transport.

Cotranslational N-terminal methionine excision and acetylation of eukaryotic proteins on ribosomes is coordinated by the nascent polypeptide-associated complex.

Malaria parasites generate metabolic energy through anaerobic glycolysis, yielding lactate that is then secreted out of the parasite cell by an unknown transporter. Here, Marchetti et al. identify and characterize a transporter that may be carrying out such a function in Plasmodium.

Synthetic pathways represent a metabolic burden on host cells. Here the authors engineer Cra-binding sites to prevent misregulation in glycerol and carotenoid overproducing E. coli strains.

Thiol-disulfide exchange is an extensively used reversible reaction in dynamic combinatorial chemistry, but usually requires long time to reach equilibrium. Here, the authors employ selenocystine as a catalyst of thiol-disulfide exchange at low temperatures and basic pH, and show that it can promote disulfide bond formation during folding of a scrambled RNase A.

Metagenomic analysis has uncovered a previously uncharacterized clade of Rubisco related to form I Rubisco found in plants and cyanobacteria. Structural and kinetic data show how this proto-form I Rubisco assembles and functions without small subunits.

Cofactor F₄₂₀ plays crucial roles in bacterial and archaeal metabolism, but its biosynthetic pathway is not fully understood. Here, the authors present the structure of one of the enzymes and provide experimental evidence for a substantial revision of the pathway, including the identification of a new intermediate.

Atmospheric methane-oxidizing bacteria constitute the sole biological sink for atmospheric methane. Here, Schmider et al. assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source, showing that these bacteria can grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air.

Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

It is unclear how cell compartmentalization emerged in prebiotic conditions. Now it is shown that a temperature gradient in a confined space can bring the core components of a cell together.

Wang et al show that the pathogen Pseudomonas aeruginosa employs two distinct acyl-CoA dehydrogenases for β-oxidation. They identify the substrate selectivity filter in each enzyme, and show that the enzymes are required for optimal virulence.

Directed evolution has emerged as a powerful tool for the identification of improved enzyme catalysts. Now, gel-shell beads are introduced as compartments that cage an enzyme with its encoding DNA, constituting a new genotype–phenotype linkage. Screening of 10⁷ gel-shell beads by flow cytometry leads to an improved phosphotriesterase bioremediation catalyst.

Calcium and redox signalling have important roles in acclimation processes. Here, the authors characterise a protein from Chlamydomonas reinhardtiithat can integrate calcium and redox-related signalling.