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Three distinct families of gut bacteria encode an unprecedented number of respiratory-like reductases per genome to perform anaerobic respiration of biomedically relevant substrates.

Homarine is a ubiquitous, phytoplankton-derived metabolite that is broken down by widely distributed and diverse marine bacteria containing a conserved homABCDER operon.

A flavin-dependent halogenase with a remarkable preference for iodination has now been discovered. The halogenase (VirX1) was discovered using a bioinformatics-based approach and comes from a cyanophage. Structural characterization and kinetic studies show that VirX1 possesses broad substrate tolerance, making it an attractive tool for synthesis.

NOXs are vital ROS-producing enzymes with roles in cell function and cancer. Here the authors combine computational and experimental methods to validate inhibitors for human NOX enzymes, opening avenues for redox biology-related cancer drug development.

Label-free two-photon fluorescence imaging of 3D engineered human brain tissue models with neurons, astrocytes, and microglia integrates spectral and FLIM analyses to reveal signatures of metabolic function and oxidative stress.

Assembled helical maquettes have been used to mimic basic oxidoreductase activities, but the requisite design symmetry limited advanced functions. Construction of a single-chain protein now enables intra- and interprotein electron transfer and complex cofactor interactions at rates comparable to those of natural proteins.

Inversion of C3 stereochemistry of monoterpenoid indole alkaloids (MIAs) has to occur at some point during their biosynthesis; however, the mechanism has remained unresolved. Here, the authors report an oxidase–reductase enzyme pair encoded within a gene cluster and demonstrate their collaborative role in inverting MIA C3 stereochemistry.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

Cryptochrome 4 from the night-migratory European robin displays magnetically sensitive photochemistry in vitro, in which four successive flavin–tryptophan radical pairs generate magnetic-field effects and stabilize potential signalling states.

Myxobacteria, particularly Sorangium strains, are rich sources of bioactive natural products but are challenging to genetically engineer. Here, the authors present an efficient electroporation method for multiple Sorangium strains and reveal a revised model of ambruticin biosynthesis.

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, the authors identify a thermosensitive enzyme that synthesizes c-di-GMP and modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa.

The gbu gene cluster, present in the human gut microbiota member Emergencia timonensis, converts γ-butyrobetaine (γBB) to trimethylamine in the conversion of dietary l-carnitine, which is found in red meat, to the proatherosclerotic metabolite trimethylamine-N-oxide. Individuals with high plasma γBB levels had increased risk of cardiovascular events.

An RNA aptamer and a ribozyme are both observed to retain a surprising degree of activity despite backbone heterogeneity caused by the presence of non-natural 2′–5′ phosphodiester linkages. These results suggest that absolute regioselectivity of non-enzymatic replication may not have been required for the emergence of RNA as the first biopolymer.

How epigenetic regulation affects pancreatic development is unclear. Here, the authors show that the histone demethylase LSD1 regulates the epigenetic state of developmental enhancers during pancreatic specification and controls how these enhancers respond to extracellular signals, namely retinoic acid.

A non-contact wearable device that defines and modulates a microclimate adjacent to the skin can measure incoming and outgoing streams of vapourized substances, offering valuable insights into physiological health, wound healing and environmental exposures.

Microbial bioelectronic sensors offer rapid and cost-effective chemical monitoring by generating electrical signals. However, deploying such sensors in the field remains challenging. This Review proposes interdisciplinary solutions and integrates advances in chassis selection, genetic modification, material engineering and device fabrication.

Here, via applying metagenomics and metabolomics analyses, the authors show that fecal microbiota composition and microbiota-derived metabolites predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection, suggesting the gut-lung axis to play an important role in the recovery from COVID-19.

The underlying mechanisms structuring dissolved organic matter (DOM) composition and reactivity in rivers remain poorly quantified. Here, the authors pair mass spectrometry and fluorescence spectroscopy to show that hydrology and river geomorphology both shape molecular patterns in DOM composition.

Mesenchymal Stromal Cells are hard to expand whilst retaining immunomodulatory properties due to spontaneous differentiation and ageing in culture. Here, the authors describe a mechanotransductive link between metabolism and functional activity and identify bioactive metabolites to expand functional MSCs at cell therapy scale.

Inspired by the art of kirigami, a haptic device based on a miniaturized electromechanical structure combined with skin as an elastic, energy-storing element demonstrates bioelastic state recovery and can be used in sensory substitution.

Crystal structures of mammalian CRY2, one of the cryptochrome flavoproteins that have light-independent functions at the core of the circadian clock, show that it binds FAD dynamically and that the F-box protein FBXL3 captures CRY2 by occupying its FAD-binding pocket and burying its PER-binding interface.

OP9 is a yet-uncultivated bacterial lineage found in anaerobic environments. Dodsworth et al. use single-cell genomics and metagenomics to construct two near-complete OP9 genomes, revealing a fermentative metabolism and supporting the designation of OP9 as candidate phylum 'Atribacteria'.

Schwannomas are regularly treated with radiotherapy, but the molecular effects on these tumours and their microenvironment remain unclear. Here, the authors show that radiotherapy can induce epigenetic reprogramming and immune infiltration in schwannomas, and develop the snARC-seq approach to analyse the epigenomic evolution at the single-cell level.

Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.

While mechanisms have been proposed for the prebiotic nucleotide synthesis, these require separate (and potentially incompatible) routes for pyrimidines and purines. Here the authors show that both of these classes of molecules can be formed by a divergent synthesis from a common prebiotic precursor.

NADPH oxidase NOX2 produces superoxide, a reactive oxygen species essential in innate immunity. Here, the authors reveal the structure of the NOX2 core, rationalize disease-causing mutations, and suggest avenues for selective NOX2 pharmacological modulation.

Mupirocin is a clinically important antibiotic, but the biosynthesis of its tetrahydropyran moiety—an oxygen heterocycle essential for its bioactivity—has remained elusive. Here, Willis, Crump and co-workers report an enzymatic reaction cascade catalysing this ring formation from a non-activated C–H bond.

The role that cellular bioenergetics plays in the early stages of Alzheimer’s disease is poorly understood. Here the authors describe structures of key OXPHOS assembly proteins, providing insights into how these pathways are interlinked and regulated.

Combined use of microcrystal electron diffraction and genome mining for biosynthetic gene clusters enables the rapid structural elucidation of natural products, including a newly discovered 2-pyridone compound and a revised structure of fischerin.

Functional proteins involved in methanogenesis and organic matter degradation in a natural gas well are from commonly identified groups of residential metagenome-assembled genomes, according to a metaproteomic, metagenomic, and geochemical analyses of Antrim Shale well water, Michigan, USA.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Mechanism-based small-molecule inhibitors targeting a gut microbial enzyme lower circulating levels of the prothrombotic metabolite trimethylamine-N-oxide and suppress diet-induced thrombosis in mice.

Leaf rust is an economically significant disease of barley. Here the authors describe cloning of the barley Rph3 leaf rust resistance gene and reveal it encodes a predicted transmembrane protein that is expressed upon infection by Rph3-avirulent Puccinia hordei isolates.

Pathway docking (in silico docking of metabolites to several enzymes and binding proteins in a metabolic pathway) enables the discovery of a catabolic pathway for the osmolyte trans-4-hydroxy-l-proline betaine.

Elizabethkingia anophelis is an emerging pathogen of high antimicrobial resistance. Perrin and colleagues sequenced isolates of a 2015/2016 E. anophelis outbreak in Wisconsin and found substantial genetic diversity, accelerated evolutionary rate and a disruptive mutation in the DNA repair gene mutY.

The potential of therapeutically targeting RNA structures with small molecules is being increasingly recognized. Here, Disney and colleagues review strategies to identify, validate and optimize small-molecule RNA binders. Examples of existing RNA-targeted small molecules, as well as challenges and future directions in the field, are discussed.

Light-inducible dimerization tags are engineered to rapidly recruit proteins to precise points in living yeast and mammalian cells. The affinities and response time of the interactions are tunable, and the authors used the system to activate cell signaling and to direct cell polarization in yeast.

Protein modules that dimerize rapidly upon exposure to light are reported. They permit light-induced control of dimerization of fused protein targets and can be manipulated with two-photon illumination for experiments in thick samples and in vivo.

Most cyanobacteria are oxygenic photoautotrophs, and fermenters under dark anoxic conditions. Here, the authors analyse genomic sequences of related uncultivated bacteria, inferring their metabolic potential, and supporting that their common ancestor was an anaerobe capable of fermentation and H₂ metabolism.

KDM5 histone demethylases promote the survival of drug-tolerant persister (DTP) cells in certain cancers. CPI-455, a chemical probe specific for KDM5, elevates cellular H3K4 methylation levels and reduces DTP cell numbers, suggesting that KDM5 is a viable target for cancer combination treatment.

Accurate, spatiotemporally resolved monitoring of environments and ecosystems serves as the starting point to both identify and remedy natural or anthropogenic environmental hazards. This Review covers materials science advances supporting a new paradigm in environmental sensing: distributed networks of sensing elements capable of system-level profiling with the possibility of harmless environmental resorption after a predetermined recording period.

Soft biological composites have great potential in areas such as artificial tissue constructs and bio-integrated devices, but receive little attention. Here, the authors design soft biomimetic materials that can precisely reproduce the non-linear mechanics of relevant biological materials.

By applying quantitative chemical cross-linking technologies, the authors show that changes in the mitochondrial interactome of the skeletal muscle contribute to mitochondrial functional decline in female mice.

Five current human African trypanosomiasis drugs are used for genome-scale RNA interference target sequencing screens in Trypanosoma brucei, and reveal the transporters, organelles, enzymes and metabolic pathways that function to facilitate antitrypanosomal drug action.

Blocking the enzyme KMO with a small molecule reduces the levels of toxic tryptophan metabolites and reduces multiple extrapancreatic organ failure in a rat model of acute pancreatitis.