Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Previous genetically encoded H2O2 probes are based on reversible thiol oxidation. Here, a heme peroxidase is introduced as a thiol-independent H2O2 probe. APEX2 converts H2O2 into fluorescent or luminescent signals, allowing its quantification.

    • Mohammad Eid
    • , Uladzimir Barayeu
    •  & Tobias P. Dick

  • Article
    | Open Access

    Hemiacetal compounds are valuable building blocks in synthetic chemistry, but difficult to obtain by enzymatic synthesis. Here, the authors use reaction engineering of an immobilized unspecific peroxygenase from Agrocybe aegerita for selective C-H bond oxyfunctionalisation of environmentally significant cyclic ethers to chiral cyclic hemiacetals.

    • Xiaofeng Han
    • , Fuqiang Chen
    •  & Wuyuan Zhang

  • Article
    | Open Access

    In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.

    • Anne M. Kiirikki
    • , Hanne S. Antila
    •  & O. H. Samuli Ollila

  • Article
    | Open Access

    Specialized pro-resolving mediators (SPM) are involved in the reprogramming of immune responses. Here the authors show that resolvin (RvT) 4 limits the progression of vascular disease in mouse models of arthritis exacerbated atherosclerotic inflammation.

    • Mary E. Walker
    • , Roberta De Matteis
    •  & Jesmond Dalli

  • Article
    | Open Access

    Conventional CRISPR-based approaches to monitor genomic loci can be hampered by high background and nonspecific nucleolar signal. Here, the authors propose a fluorogenic CRISPR (fCRISPR) tool that allows for high-contrast and sensitive imaging of genomic DNA.

    • Zhongxuan Zhang
    • , Xiaoxiao Rong
    •  & Xing Li

  • Article
    | Open Access

    Proteins labelled site-specifically with small molecules are valuable assets for chemical biology and drug development. Here, the authors report Baylis Hillman orchestrated protein aminothiol labelling (BHoPAL), a bioconjugation strategy for specific labelling of the 1,2-aminothiol moiety and combine it with a lipoic acid ligase-based technology to achieve labelling at any desired site within proteins.

    • Mudassir H. Mir
    • , Sangeeta Parmar
    •  & Dimpy Kalia

  • Article
    | Open Access

    Succinate dehydrogenase converts malate to enoloxaloacetate, a metabolically inactive and inhibitory side product of the TCA cycle. Here, Zmuda et al. describe a conserved metabolite damage repair enzyme that can remove enol-oxaloacetate and is critical for efficient aerobic respiration.

    • Anthony J. Zmuda
    • , Xiaojun Kang
    •  & Thomas D. Niehaus

  • Article
    | Open Access

    In vivo detection of cell senescence remains a challenge in aging research. This work introduces a novel fluorogenic probe for β-Gal activity that is excreted in urine, providing a simple diagnosis method to estimate the systemic load of senescent cells during aging and senolytic interventions.

    • Sara Rojas-Vázquez
    • , Beatriz Lozano-Torres
    •  & Ramón Martínez-Máñez

  • Article
    | Open Access

    No consensus exists on the computationally tractable use of dynamic models for strain design. To tackle this, the authors report a framework, nonlinear-dynamic-model-assisted rational metabolic engineering design, for efficiently designing robust, artificially engineered cellular organisms.

    • Bharath Narayanan
    • , Daniel Weilandt
    •  & Vassily Hatzimanikatis

  • Article
    | Open Access

    The mechanical dysregulation of cells is associated with several diseases and strategies to deliver drugs based on the “mechanical phenotype” of a cell are desirable. Here, the authors design and characterize DNA mechanocapsules comprised of DNA tetrahedrons that are force responsive, and showed they can encapsulate macromolecular cargo and release it upon application of force.

    • Arventh Velusamy
    • , Radhika Sharma
    •  & Khalid Salaita

  • Article
    | Open Access

    Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

    • Arun Chandramohan
    • , Hubert Josien
    •  & Anthony W. Partridge

  • Article
    | Open Access

    Ajmaline is an antiarrhythmic monoterpenoid indole alkaloid produced by the root of Rauwolfia serpentina. Here, the authors complete the ajmaline biosynthetic pathway by identifying two reductases and two esterases, and achieve the de novo ajmaline biosynthesis by engineering Baker’s yeast.

    • Jun Guo
    • , Di Gao
    •  & Yang Qu

  • Article
    | Open Access

    IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.

    • Theresa Kissel
    • , Veerle F. A. M. Derksen
    •  & René E. M. Toes

  • Article
    | Open Access

    Much is still unknown of the evolution of animal metabolic enzymes. This study describes a new enzyme family bridging the production of polyketides and membrane lipids. This expands the known biochemical repertoire of animals for making ecologically and biomedically important natural products.

    • Zhenjian Lin
    • , Feng Li
    •  & Eric W. Schmidt

  • Article
    | Open Access

    Avapritinib, a potent inhibitor, offers hope for D842V-mutant GIST patients with high response rates; however, resistance and side effects remain challenges. Here, crystal structures shed light on this and reveal a Gα-pocket for drug development.

    • A. Teuber
    • , T. Schulz
    •  & D. Rauh

  • Article
    | Open Access

    Coacervate droplets have potential as components for cell-like materials, but are limited by complex molecular structure and control of the internal microenvironment. Here, the authors report stable dipeptide-based coacervates with a microenvironment for the encapsulation of hydrophobic species.

    • Shoupeng Cao
    • , Tsvetomir Ivanov
    •  & Lucas Caire da Silva

  • Article
    | Open Access

    One-carbon substrates are attractive feedstocks for circular bioeconomy. Here, the authors design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, demonstrate the activity of the core reactions in E. coli, and show its integration with pathway reactions existed in pentose phosphate pathway and glycolysis.

    • Tong Wu
    • , Paul A. Gómez-Coronado
    •  & Hai He

  • Review Article
    | Open Access

    As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. In this review, the authors outline design strategies for the DNA, RNA, and protein-level circuits and the hybrid “multi-level” circuits.

    • Yuanli Gao
    • , Lei Wang
    •  & Baojun Wang

  • Article
    | Open Access

    Metabolic oligosaccharide engineering (MOE) is a classical strategy for carbohydrate perception but suffers from glycan quantification. Here the authors develop a selenium-based metabolic oligosaccharide engineering strategy (SeMOE), based on elemental analysis, to quantitatively detect and visualize glycans both in vitro and in vivo.

    • Xiao Tian
    • , Lingna Zheng
    •  & Ran Xie

  • Article
    | Open Access

    Prediction of enzyme kinetic parameters is essential for designing and optimising enzymes for various biotechnological and industrial applications. Here, authors presented a prediction framework (UniKP), which improves the accuracy of predictions for three enzyme kinetic parameters.

    • Han Yu
    • , Huaxiang Deng
    •  & Xiaozhou Luo

  • Article
    | Open Access

    The molecular composition of the axon initial segment (AIS) is not well defined. Here, the authors used a ratiometric immunoproximity labeling strategy on fixed wild-type rat neurons to identify the AIS proteome, including the scaffolding protein SCRIB.

    • Wei Zhang
    • , Yu Fu
    •  & Peng Zou

  • Article
    | Open Access

    GPCRs include inactive and active states. 19F-NMR and stopped-flow fluorescence kinetic assays reveal that neurotensin activates the prototypical peptide-binding GPCR, neurotensin receptor 1, through an induced-fit mechanism, where ligand binding precedes receptor conformational changes.

    • Kazem Asadollahi
    • , Sunnia Rajput
    •  & Paul R. Gooley

  • Article
    | Open Access

    Peptide drug manufacturing commonly uses large amounts of hazardous solvents primarily due to multiple washings after each step. Here, the authors introduce the concept of a completely wash-free methodology that enables up to 95% waste reduction.

    • Jonathan M. Collins
    • , Sandeep K. Singh
    •  & Christopher L. Houser

  • Article
    | Open Access

    Stress-hormone receptors are important therapeutic targets for many diseases but the currently clinically approved inhibitor lacks specificity. Here the authors present a stress hormone receptor depletion tool that differs in its mode of action making it specific in counteracting the effects of stress.

    • Mahshid Gazorpak
    • , Karina M. Hugentobler
    •  & Katharina Gapp

  • Article
    | Open Access

    The treatment of Parkinson’s disease (PD) is hampered by the lack of effective blood–brain barrier (BBB) traversing drugs. Here, the authors report nanozyme-integrated metal-organic frameworks with antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for PD treatment.

    • Wei Jiang
    • , Qing Li
    •  & Kelong Fan

  • Article
    | Open Access

    The cells of our bodies use chemical signals to talk with each other. Here the authors describe a class of signaling molecules called “capped peptides” that may mediate cell-cell communication. Unlike other peptides, capped peptides have unique chemical modifications which make them potentially more active and stable.

    • Amanda L. Wiggenhorn
    • , Hind Z. Abuzaid
    •  & Jonathan Z. Long

  • Article
    | Open Access

    Ameliorating or preventing signatures of aging in humans using natural compounds is an exciting area of research. Here the authors isolate a previously unknown phytochemical from carrots which activates defence mechanisms against oxidative stress and extends lifespan in worms, and improves glucose metabolism, promotes exercise capacity, and protects from frailty at higher age in mice.

    • Carolin Thomas
    • , Reto Erni
    •  & Michael Ristow

  • Article
    | Open Access

    Type II polyketide synthases (PKSs) normally synthesize polycyclic aromatic compounds, but the potential for the synthesis of further diverse skeletons remains under investigated. Here, the authors report the discovery of the type II PKS machinery for the biosynthesis of a five-membered nonaromatic skeleton contained in the nonproteinogenic amino acid cispentacin and the plant toxin coronatine.

    • Genki Hibi
    • , Taro Shiraishi
    •  & Tomohisa Kuzuyama

  • Article
    | Open Access

    Non-addictive treatments for pain are much needed. Here, the authors identify in vivo active leads for inflammatory pain using large library docking against the EP4 prostaglandin receptor.

    • Stefan Gahbauer
    • , Chelsea DeLeon
    •  & Brian K. Shoichet

  • Article
    | Open Access

    Direct, site-specific methods of protein functionalization are of interest, but challenging due to difficulty in chemically differentiating a single site within a large protein. Here, the authors develop a Copper Assisted Sequence-specific conjugation Tag (CAST) method to achieve rapid, site-specific protein backbone chemical modification with pinpoint accuracy, and prepare various on-demand modified recombinant proteins using CAST.

    • Mengzhun Guo
    • , Kai Zhao
    •  & Bobo Dang

  • Article
    | Open Access

    Protocell’s survival and fitness under prebiotic radiations are elusive. Here, the authors present a radioresistant protocell model based on the assembly of two types of coacervate droplets, formed through interactions of inorganic polyphosphate with manganese and cationic tripeptide, respectively, and show that nonenzymatic Mn antioxidants are essential for its resistance to radiation.

    • Shang Dai
    • , Zhenming Xie
    •  & Bing Tian

  • Article
    | Open Access

    Chemotherapy-induced peripheral neuropathy (CIPN) represents a major reason for discontinuation of treatment. Here, the authors show that LEI-515, a peripherally restricted monoacylglycerol lipase inhibitor, suppresses CIPN without inducing central nervous system side effects or physical dependence.

    • Ming Jiang
    • , Mirjam C. W. Huizenga
    •  & Mario van der Stelt

  • Article
    | Open Access

    Unbiased chemical biology strategies for direct readout of small molecule protein interactomes provide advantages over target-focused approaches. Here, the authors describe the BioTAC system, a network-scale small molecule guided proximity labeling platform, to rapidly identify ligand-target interactomes.

    • Andrew J. Tao
    • , Jiewei Jiang
    •  & Fleur M. Ferguson

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