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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 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.

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.

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.

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.

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.

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.

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 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.

The authors report observations of recently formed dust and molecular gas in the atmosphere of IRC+10°216 and interpret HCN, SiS and SiC₂ lines as large convective cells in the photosphere, as seen in Betelgeuse.

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.

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.

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.

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.

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.

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.

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.

How do low-mass binaries age? Astronomers have constrained a tight, circular orbit of a close-in companion around a dying giant star, raising new questions about how tidal forces shape binary orbits in the final phases of stellar evolution.

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.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

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.

Affinity chromatography allows for the separation of biomolecules such as proteins, based on a change in the chemical solvent composition and the resulting impacts on ligand binding. Here, authors introduce a physical principle by exploiting the light-dependent interaction between the Azo-tag and an α- CD chromatography matrix.

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.

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.

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.

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

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.

Plant pathogens translocate type III effector (T3E) proteins that may be recognized by plants to trigger immunity. Here, the authors show that the Xanthomonas T3E XopH possesses a novel 1-phytase activity that is required for XopH-mediated immunity of plants carrying the Bs7 resistance gene.

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.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

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

Ubiquitin modification also occurs in archaea. Here, the authors characterize an archaeal ancestral ubiquitination system, present the crystal structure of the archaeal deubiquitinase Rpn11 from Caldiarchaeum subterraneum bound to ubiquitin and provide insights into evolutionary relationships.

A combination of structural and protein-chemistry approaches along with phylogenetic analyses provide insights into the specific activities of mouse tubulin tyrosine ligase-like enzymes as initiases or elongases of glutamylation.

The COP9 signalosome (CSN) complex regulates cullin–RING E3 ubiquitin ligases—the largest class of ubiquitin ligase enzymes, which are involved in a multitude of regulatory processes; here, the crystal structure of the entire human CSN holoenzyme is presented.

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

X-ray crystallographic analyses of KDM5B provide a view of the enzyme's iron(II)- and 2-oxoglutarate-containing catalytic core, and structures of KDM5B complexes with small-molecule inhibitors reveal selectivity profiles for multiple compound chemotypes.

The ability to induce metabolic pathways in response to a changing environment is an important component of bacterial fitness. Bartl et al. identify optimal programmes for metabolic pathway activation depending on protein synthesis capacity constraints, and demonstrate their impact on operonic organization.

A genome-wide CRISPR interference screen shows that a signalling pathway involving OMA1, DELE1 and the eIF2α kinase HRI relays mitochondrial stress to the cytosol to trigger the integrated stress response.

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.

Alien species of animals and plants can invade new regions of the earth. This study performs a global analysis of temporal dynamics and spatial patterns of alien species introductions over the past 200 years, and reports no saturation in the rate at which these invasion are increasing.

The introduction of fluorine into a drug molecule can alter the biological responses to it, including modulating bioavailability, pharmacokinetics and selectivity. Now, a hybrid polyketide/fatty acid synthase multienzyme has been designed to incorporate fluorinated precursors during polyketide biosynthesis in an approach that provides new chemoenzymatic access to fluorinated natural compounds.

Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.