Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Constructing polymer-based mimics on the surface of cells has potential to manipulate cell behavior, but precise control of grafting sites is challenging. Here, the authors report a method for site selected radical polymerization on cell surfaces by metabolic labelling.

    • Yihong Zhong
    • , Lijia Xu
    •  & Huangxian Ju

  • Article
    | Open Access

    Sufficient supply of sulfonate group donor is critical to biomanufacturing of the sulfate containing compounds. Here, the authors engineer two sulfonate group donor regeneration systems, including 3'-phosphoadenosine-5'-phosphosulfate and the newly discovered 5'-phosphosulfate, to boost biosynthesis of sulfated compounds.

    • Ruirui Xu
    • , Weijao Zhang
    •  & Zhen Kang

  • Article
    | Open Access

    Mapping protein turnover dynamics with subcellular precision is crucial for understanding cell physiology and pathology. Here, the authors leveraged APEX2-mediated proximity labeling to develop prox-SILAC methods to profile protein turnover rates in the mitochondria and endoplasmic reticulum.

    • Feng Yuan
    • , Yi Li
    •  & Peng Zou

  • Article
    | Open Access

    Specific modification or functionalization of proteins at the C-terminus is of interest but remains challenging. Here, the authors report an approach for the efficient modification of C-terminus by fusion of the cysteine protease domain (CPD) on the C-terminus of the protein of interest, and subsequent functionalization with amine-containing molecules triggered by InsP6-mediated CPD self-cleavage.

    • Yue Zeng
    • , Wei Shi
    •  & Feng Tang

  • Article
    | Open Access

    Methylation is the dominant modification in mRNA and occurs at a variety of sites. Here, Hartstock et al. show that a clickable analogue of the key cosubstrate S-adenosyl-L-methionine (SAM) can be produced in cells, allowing for identification and mapping of different methylated nucleosides in mRNA.

    • Katja Hartstock
    • , Nadine A. Kueck
    •  & Andrea Rentmeister

  • Article
    | Open Access

    Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. Here, the authors develop a potent activator ZK53 that is highly selective on human ClpP but inactive toward bacterial ClpP proteins, and show that ZK53 causes cell cycle arrest via ClpP on lung squamous cell carcinoma cells and exhibits therapeutic effects in animal models.

    • Lin-Lin Zhou
    • , Tao Zhang
    •  & Cai-Guang Yang

  • Article
    | Open Access

    The ability to control proteins in cells and animals is important for experimental research and may have therapeutic applications. Here, the authors developed a new set of heterobifunctional small molecules based on the antibiotic trimethoprim that can degrade proteins that are genetically tagged with E. coli dihydrofolate reductase (eDHFR).

    • Jean M. Etersque
    • , Iris K. Lee
    •  & Mark A. Sellmyer

  • Article
    | Open Access

    The rational design and implementation of synthetic mammalian communication systems can unravel fundamental design principles of cell communication circuits and offer a framework for engineering of designer cell consortia with potential applications in cell therapeutics. Here the authors present a synthetic communication platform in mammalian cells based on diffusible dipeptide ligands and synthetic receptors, that is by design highly orthogonal, scalable, and programmable.

    • Anna-Maria Makri Pistikou
    • , Glenn A. O. Cremers
    •  & Tom F. A. de Greef

  • Article
    | Open Access

    Identification of molecules that induce novel interactions between proteins has been limited by the complexity of rationally designing interactions. The authors report a method to discover molecular glue-like “trimerizers” based on α-helically constrained peptides that can co-opt the surfaces of E3 ubiquitin ligases to bind therapeutically important proteins.

    • Olena S. Tokareva
    • , Kunhua Li
    •  & John H. McGee

  • Article
    | Open Access

    This study found that cnidarian animals including corals, anemones and jellyfish share a common mechanism to regulate their association with symbiotic algae. Despite evolving independently, these animals all use the same carbon-nitrogen negative feedback loop for algae control, shedding light on the repeated evolution of these marine symbiotic relationships.

    • Guoxin Cui
    • , Jianing Mi
    •  & Manuel Aranda

  • Article
    | Open Access

    Unnatural base pairing xenonucleic acids (XNAs) can be used to expand life’s alphabet beyond ATGC. Here, authors show strategies for enzymatic synthesis and next-generation nanopore sequencing of XNA base pairs for reading and writing 12-letter DNA (ATGCBSPZXKJV).

    • Hinako Kawabe
    • , Christopher A. Thomas
    •  & Jorge A. Marchand

  • Article
    | Open Access

    Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.

    • Yang Cao
    • , Huachun Liu
    •  & Bryan C. Dickinson

  • Article
    | Open Access

    In nature, α-helical peptides adopt right-handed conformations dictated by L-amino acids, but isolating one-handed α-helical peptides composed of only achiral components remains a challenge. Here, the authors achieve this by optical resolution of the corresponding racemic (quasi-)static α-helical peptide with double stapling, which effectively freezes the interconversion between the right-handed (P)- and left-handed (M)-α-helices.

    • Naoki Ousaka
    • , Mark J. MacLachlan
    •  & Shigehisa Akine

  • Article
    | Open Access

    O-acetylation is a common modification of sialic acids. Here, a library of synthetic O-acetylated sialosides made it possible to develop an ion mobility mass spectrometry (IM-MS) approach that can elucidate exact O-acetylation patterns and glycosidic linkage types of sialosides isolated from biological samples.

    • Gaёl M. Vos
    • , Kevin C. Hooijschuur
    •  & Geert-Jan Boons

  • Article
    | Open Access

    Apiosides are plant bioactive natural products containing apiose, but the details of the key apiosylation reaction in their biosynthesis are missing. Here, the authors identify the apiosyltransferase GuApiGT that could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, solve its crystal structure and obtain mutants with altered sugar selectivity.

    • Hao-Tian Wang
    • , Zi-Long Wang
    •  & Min Ye

  • Article
    | Open Access

    Nonribosomal peptides have diverse bioactivities and can possess unusual moieties at their C-terminus, such as polyamines. In this study, the authors identify a class of dodecapeptides glidonins that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus, elucidate their biosynthesis, and introduce the putrescine into the C-terminus of other nonribosomal peptides.

    • Hanna Chen
    • , Lin Zhong
    •  & Xiaoying Bian

  • Article
    | Open Access

    Heparan sulfate (HS) and chondroitin sulfate (CS) are different glycosaminoglycan chains that are attached to core proteins via the same linker tetrasaccharide, and it was unclear how core proteins are specifically modified with HS or CS. Here, the authors determine that the CS-initiating glycosyltransferase CSGALNACT2 is promiscuous, whereas the HS-initiating glycosyltransferase EXTL3 selects only certain core proteins for modification.

    • Douglas Sammon
    • , Anja Krueger
    •  & Erhard Hohenester

  • Article
    | Open Access

    Tools for high spatiotemporal control of cell-cell adhesions are lacking. Here, authors propose an optogenetic tool, opto-E-cadherin, that allows reversible control of E-cadherin-mediated cell-cell adhesions with blue light.

    • Brice Nzigou Mombo
    • , Brent M. Bijonowski
    •  & Seraphine V. Wegner

  • Article
    | Open Access

    MonCI, a flavin-dependent monooxygenase, transforms all three C = C groups in the polyene substrate into epoxides during monensin A biosynthesis. Here, the authors present the structural basis for this enzyme’s regio- and stereoselective epoxidation activity.

    • Qian Wang
    • , Ning Liu
    •  & Chu-Young Kim

  • Article
    | Open Access

    Here the authors introduce a photo-activatable-competition and chemoproteomic enrichment (PACCE) method to localize protein-RNA interfaces using photoactivatable cellular RNA to protect RNA binding regions on proteins from electrophilic purine probe labeling.

    • Andrew J. Heindel
    • , Jeffrey W. Brulet
    •  & Ku-Lung Hsu

  • Article
    | Open Access

    The study of interstitial calcium remains challenging due to scarce methodology. Here, authors present ultra-low affinity genetically encoded fluorescent biosensors for monitoring calcium in intercellular spaces in living tissues.

    • Ariel A. Valiente-Gabioud
    • , Inés Garteizgogeascoa Suñer
    •  & Oliver Griesbeck

  • Article
    | Open Access

    The ability to rationally remodel enzyme conformational landscapes to modify catalytic properties is limited. Here, the authors, using a computational procedure, redesign the conformational landscape of an aminotransferase to stabilize a less populated but reactive conformation and thereby increase catalytic efficiency with a non-native substrate.

    • Antony D. St-Jacques
    • , Joshua M. Rodriguez
    •  & Roberto A. Chica

  • Article
    | Open Access

    Solvent shielding of the amide hydrogen bond donor through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. Here, the authors show that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor through thioamide substitution, leading to improved pharmacological properties of peptide macrocycles.

    • Pritha Ghosh
    • , Nishant Raj
    •  & Jayanta Chatterjee

  • Article
    | Open Access

    Vibrio α-hemolysins (αHLs) are toxins crucial for certain bacterial infections. Here the authors reveal that calcium ions boost the activity of a specific toxin, Vibrio campbellii αHL, and uncover its calcium-dependent activation mechanism.

    • Yu-Chuan Chiu
    • , Min-Chi Yeh
    •  & Shih-Ming Lin

  • Article
    | Open Access

    Chemical catalysts that can promote physiologically important post-translational modifications acting as enzyme surrogates have not been reported. Here, the authors develop mBnA, a chemical catalyst that promotes histone lysine acylation in live cells by activating endogenous acyl-CoAs as the only acyl donors.

    • Misuzu Habazaki
    • , Shinsuke Mizumoto
    •  & Motomu Kanai

  • Article
    | Open Access

    P2X3 activation requires tightening the inner pocket of the head domain (IP-HD) following ATP binding. Here the authors demonstrate that targeting the IP-HD with allosteric small molecules presents a potential strategy for the development of therapeutics for refractory chronic cough without taste abnormalities.

    • Chang-Run Guo
    • , Zhong-Zhe Zhang
    •  & Ye Yu

  • Article
    | Open Access

    Rieske oxygenase chemistry is important for biochemical pathways, but it remains elusive how a common protein scaffold can be predictively tuned to catalyze divergent reactions. Here, the authors report a strategy that can rationally tune TsaM, a Rieske monooxygenase to catalyze dioxygenation and sequential monooxygenation reactions, and customize the reactivity of other Rieske oxygenases.

    • Jiayi Tian
    • , Jianxin Liu
    •  & Jennifer Bridwell-Rabb

  • Article
    | Open Access

    In this work, the authors report that Histidine residues play a critical role in modulating amyloid-like assembly and building active sites for Fmoc–F–F and Aβ aggregates. Aβ1-42 filaments were found to perform peroxidase-like activity to enhance oxidative stress, which might also be ascribed to the interaction mode of His and F-F.

    • Ye Yuan
    • , Lei Chen
    •  & Lizeng Gao

  • Article
    | Open Access

    Peptide-based therapeutics are promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. Here, the authors report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine chemistry, with decafluoro-diphenylsulfone.

    • Jeffrey Y. K. Wong
    • , Arunika I. Ekanayake
    •  & Ratmir Derda

  • Article
    | Open Access

    The inherent toxicity of the aromatic compounds to the chassis strain hampers further improvement of bioproduction. Here, the authors show that membrane rigidifying effect of resveratrol can be attenuated by exogenous supplementation of palmitelaidic acid or linoleic acid in fermentation of Corynebacterium glutamicum.

    • Apilaasha Tharmasothirajan
    • , Josef Melcr
    •  & Jan Marienhagen

  • Article
    | Open Access

    Here, the reaction of the suicide inhibitor sulbactam with the M. tuberculosis β-lactamase (BlaC) is investigated with time-resolved crystallography. Singular Value Decomposition is implemented to extract kinetic information despite changes in unit cell parameters during the time-course of the reaction.

    • Tek Narsingh Malla
    • , Kara Zielinski
    •  & Marius Schmidt

  • Article
    | Open Access

    Different types of lytic cell death can trigger an anti-tumor immune response. Here the authors report the design of a near infrared light controllable micron-scale oncolytic system, triggering lipid peroxidation and lytic cell death in tumors as well anti-tumor immunity in preclinical cancer models.

    • Zhigui Zuo
    • , Hao Yin
    •  & Qinyang Wang

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