Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Ribonucleoside monophosphates are incorporated by DNA polymerases into double-stranded DNA. Here, the authors use ribose-seq and Ribose-Map techniques to reveal that signatures and patterns of ribonucleotide incorporation in yeast mitochondrial and nuclear DNA show preference for cytosine and guanosine preceded by deoxyadenosine.

    • Sathya Balachander
    • , Alli L. Gombolay
    •  & Francesca Storici

  • Article
    | Open Access

    Protein arginine methyltransferases (PRMTs) are increasingly recognized as potential therapeutic targets but PRMT7 remains an understudied member of this enzyme family. Here, the authors develop a chemical probe for PRMT7 and apply it to elucidate the role of PRMT7 in the cellular stress response.

    • Magdalena M. Szewczyk
    • , Yoshinori Ishikawa
    •  & Dalia Barsyte-Lovejoy

  • Article
    | Open Access

    Lactazole A is a thiopeptide from Streptomyces lactacystinaeus, encoded by a compact 9.8 kb biosynthetic gene cluster. Here, the authors show a platform for in vitro biosynthesis of lactazole A via a combination of a flexible in vitro translation system with recombinantly produced lactazole biosynthetic enzymes.

    • Alexander A. Vinogradov
    • , Morito Shimomura
    •  & Hiroyasu Onaka

  • Article
    | Open Access

    Antibodies conjugated to bioactive compounds can allow targeted delivery of therapeutics. Here the authors present a strategy for fusing nanobodies to suboptimal GPCR peptide ligands to potently and selectively activate receptors.

    • Ross W. Cheloha
    • , Fabian A. Fischer
    •  & Hidde L. Ploegh

  • Article
    | Open Access

    Cell-free lysates are a major platform for in vitro protein production but batch-to-batch variation makes production difficult to predict. Here the authors develop an active learning approach to optimising buffer conditions to bring homemade lysates up to commercial production potential.

    • Olivier Borkowski
    • , Mathilde Koch
    •  & Jean-Loup Faulon

  • Article
    | Open Access

    Combining genome mining and heterologous expression in a genetically tractable host can lead to bioactive natural products discovery and production. Here, the authors employ this strategy for new decalin-containing diterpenoid pyrenes production by expressing native, extended, and shunt pathways in Aspergillus oryzae.

    • Kento Tsukada
    • , Shono Shinki
    •  & Teigo Asai

  • Article
    | Open Access

    Inhibitors of the BET family proteins are limited by their potency and oral bio-availability. Here, the authors report a new BET inhibitor, NHWD-870, with improved potency compared to previous BET inhibitors, and show that it suppresses BRD4 and targets tumour associated macrophages.

    • Mingzhu Yin
    • , Ying Guo
    •  & Qin Yan

  • Article
    | Open Access

    NF-κB signalling involves the scaffold protein NEMO, which can be bound by the oncoprotein vFLIP to promote cell survival and oncogenic transformation. Here the authors rationally engineer a tertiary protein mimic of NEMO to disrupt the vFLIP-NEMO interaction to induce cell death.

    • Jouliana Sadek
    • , Michael G. Wuo
    •  & Paramjit S. Arora

  • Article
    | Open Access

    The formation of C-C bonds in fatty acid and polyketide biosynthesis depends on β-ketoacyl-acyl carrier protein (ACP) synthases (KSs). Here, the authors present structures of E.coli KSs bound to substrate mimetic bearing ACPs, providing insights into the catalytic mechanism underlying C-C bond forming reactions.

    • Jeffrey T. Mindrebo
    • , Ashay Patel
    •  & Michael D. Burkart

  • Article
    | Open Access

    Upon transition to stationary phase or upon stress, bacteria limit protein synthesis through small inhibitory proteins that bind the ribosome. Here the authors decipher the interaction mode of the bacterial ribosome silencing factor (RsfS) at atomic details to provide an in depth view of how it shutdowns ribosomes.

    • Iskander Khusainov
    • , Bulat Fatkhullin
    •  & Marat Yusupov

  • Article
    | Open Access

    Identifying kinases responsible for specific phosphorylation events remains challenging. Here, the authors leverage kinase inhibitor profiles for the identification of kinase-substrate site pairs in cell extracts, developing a method that can identify the enzymes responsible for unassigned phosphorylation events.

    • Nikolaus A. Watson
    • , Tyrell N. Cartwright
    •  & Jonathan M. G. Higgins

  • Article
    | Open Access

    How nature creates 1,2,3-triazole ring is a relevant question to N-N bond biosynthesis. Here, the authors report the biosynthetic route to the triazole-bearing antimetabolite 8-azaguanine and reveal that this can be assembled through an enzymatic and non-enzymatic cascade, in which nitric oxide is used as a building block.

    • Guiyun Zhao
    • , Yuan-Yang Guo
    •  & Yi-Ling Du

  • Article
    | Open Access

    The spectra of light used by photosynthetic organisms are determined by their pigmentation colour palettes. Here Liu et al. show that a genetically-encoded chimera of light-harvesting proteins from plants and reaction centres from purple bacteria allows for polychromatic solar energy harvesting.

    • Juntai Liu
    • , Vincent M. Friebe
    •  & Michael R. Jones

  • Article
    | Open Access

    Granadaene, produced by Group B Streptococcus (GBS), is a long polyene lipid involved in cellular toxicity and hemolytic activity. Here, the authors synthesize and characterize granadaene-like compounds and show that a non-toxic analog diminishes GBS infection in mice when incorporated into a vaccine formulation.

    • Blair Armistead
    • , Pilar Herrero-Foncubierta
    •  & Lakshmi Rajagopal

  • Article
    | Open Access

    Biosynthetic mechanism for the type 2 diabetes treatment drug acarbose is not fully revealed. Here, the authors show that shunt pathways and inefficient amino-deoxyhexose biosynthesis lead to 1-epi-valienol and valienol accumulation, and minimizing the flux to these shunt products can increase acarbose titer in Actinoplanes species.

    • Qinqin Zhao
    • , Yuchang Luo
    •  & Zixin Deng

  • Article
    | Open Access

    O-alkylation of carboxylates by alkyl halides has only been observed transiently in enzymatic processes. Here, the authors show a carboxylate alkylating enzyme, BrtB, that catalyzes C-O bond formation between free fatty acids and secondary alkyl chlorides.

    • João P. A. Reis
    • , Sandra A. C. Figueiredo
    •  & Pedro N. Leão

  • Article
    | Open Access

    Most epigenetic regulator inhibitors target tunnels of active sites, rather than the peptide binding groove, leading to concerns with low selectivity. Here the authors use an amber obligate phage library to rapidly identify isoform-selective inhibitors of SIRT2.

    • Jeffery M. Tharp
    • , J. Trae Hampton
    •  & Wenshe Ray Liu

  • Article
    | Open Access

    Hepatocytes grown in a dish are immature and do not metabolize compounds as a real liver would. Here, the authors supply stem cell-derived hepatocytes with amino acids at a higher concentration than nutritionally necessary, changing the metabolism of these cells, making them more mature and useful for drug screening and toxicity studies.

    • Ruben Boon
    • , Manoj Kumar
    •  & Catherine M. Verfaillie

  • Article
    | Open Access

    Optogenetic manipulation of protein localisation in cells involves the creation of fusions that can influence activity. Here the authors develop a near-infrared light-responsive aptamer-based system to regulate the nuclear-cytoplasmic shuttling of NF-κB subunit RelA.

    • Sitao Xie
    • , Yulin Du
    •  & Weihong Tan

  • Article
    | Open Access

    Karrikins are germination stimulants perceived by KAI2 in Arabidopsis. Here the authors show that Brassica tournefortii, a close relative to Arabidopsis, has multiple copies of KAI2 with amino acid substitutions that confer responsiveness to the specific karrikin compounds found in wildfire smoke.

    • Yueming Kelly Sun
    • , Jiaren Yao
    •  & Mark T. Waters

  • Article
    | Open Access

    Sensitive diagnostic tools for bacterial infections of wounds and surgical sites are necessary to enable early detection and determine optimal means of treatment. Here, the authors develop a fluorescent and optoacoustic probe based on a maltotriose scaffold, which is selectively taken up by gram-positive and gram-negative bacteria.

    • Aimen Zlitni
    • , Gayatri Gowrishankar
    •  & Sanjiv Sam Gambhir

  • Article
    | Open Access

    Recent studies revealed that G protein-coupled receptors rapidly interconvert between multiple states. Here, authors use the kappa opioid receptor (KOR) and show how two state-dependent nanobodies provide real-time reporting of ligand stabilized states with KOR and other GPCRs.

    • Tao Che
    • , Justin English
    •  & Bryan L. Roth

  • Article
    | Open Access

    Bacillus thuringiensis israelensis (Bti) produces the naturally-crystalline proteinaceous toxin Cyt1Aa that is toxic to mosquito larvae. Here the authors grow recombinant nanocrystals of the Cyt1Aa protoxin in vivo and use serial femtosecond crystallography to determine its structure at different redox and pH conditions and by combining their structural data with further biochemical, toxicological and biophysical analyses provide mechanistic insights into the Cyt1Aa bioactivation cascade.

    • Guillaume Tetreau
    • , Anne-Sophie Banneville
    •  & Jacques-Philippe Colletier

  • Article
    | Open Access

    Aspergillus fungi classified within the section Flavi include harmful and beneficial species. Here, Kjærbølling et al. analyse the genomes of 23 Flavi species, showing high genetic diversity and potential for synthesis of over 13,700 CAZymes and 1600 secondary metabolites.

    • Inge Kjærbølling
    • , Tammi Vesth
    •  & Mikael R. Andersen

  • Article
    | Open Access

    Metabolic engineering is often hampered by non-linear kinetics and allosteric regulatory mechanisms. Here, the authors construct a quantitative model for the pentose degradation Weimberg pathway in Caulobacter crescentus and demonstrate its biotechnological applications in cell-free system and standard metabolic engineering.

    • Lu Shen
    • , Martha Kohlhaas
    •  & Bettina Siebers

  • Article
    | Open Access

    Nicotinamide adenine dinucleotide and coenzyme A serve as a 5′-cap of prokaryotic RNA. Here the authors report that methylated and non-methylated dinucleoside polyphosphates (NpnNs) exist as Escherichia coli RNA caps which can be cleaved by 5′-pyrophosphohydrolase (RppH) and bis(5′-nucleosyl)-tetraphosphatase (ApaH).

    • Oldřich Hudeček
    • , Roberto Benoni
    •  & Hana Cahová

  • Article
    | Open Access

    Glucuronoyl esterases have the potential to be used in the biocatalytic conversion of lignin-carbohydrate complexes to obtain pure lignin for downstream biofuel conversion. Here the authors present a detailed structural analysis of the glucuronoyl esterase from Cerrena unicolor, providing the basis for its activity on natural substrate and for how lignin can be selectively separated from lignocellulosic materials.

    • Heidi A. Ernst
    • , Caroline Mosbech
    •  & Sine Larsen

  • Article
    | Open Access

    Many reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Here the authors report 3-bromo-5-methylene pyrrolones as a simple, robust and versatile class of reagents for cysteine-specific protein modification.

    • Yingqian Zhang
    • , Chuanlong Zang
    •  & Chuanzheng Zhou

  • Article
    | Open Access

    Lytic polysaccharide (mono)oxygenases (LPMOs) perform oxidative cleavage of polysaccharides. Here, the authors showed that the light-driven activity of LPMOs is dependent on hydrogen peroxide availability and can be controlled via the light intensity provided.

    • Bastien Bissaro
    • , Eirik Kommedal
    •  & Vincent G. H. Eijsink

  • Article
    | Open Access

    Formylpeptide receptors (FPRs) are a class of chemotactic G protein-coupled receptors (GPCRs) that recognize pathogen- and host-derived formylpeptides. Here the authors report the 3.17 Å cryo-EM structure of the human FPR2-Gi signaling complex with a bound peptide agonist and in combination with computational docking and MD simulations provide mechanistic insights into formylpeptide recognition by FPRs.

    • Youwen Zhuang
    • , Heng Liu
    •  & Cheng Zhang

  • Article
    | Open Access

    Protein tyrosine phosphatases regulate many cellular processes but are difficult to study in their native context. Here the authors develop an approach for using light to control the activity of a disease-relevant phosphatase without interfering with its native cellular organization.

    • Akarawin Hongdusit
    • , Peter H. Zwart
    •  & Jerome M. Fox

  • Article
    | Open Access

    Engineering mammalian cellular functions requires a toolkit of orthogonal and well-characterized genetic components. Here the authors develop COMET: an ensemble of transcription factors, promoters, and accompanying models for the design and construction of genetic programs.

    • Patrick S. Donahue
    • , Joseph W. Draut
    •  & Joshua N. Leonard

  • Article
    | Open Access

    Validating crosslinking-mass spectrometry workflows is hampered by the lack of a ground truth to assess the robustness of the crosslink identifications. Here, the authors present a synthetic library of crosslinked peptides, enabling unambiguous discrimination of correct and incorrect crosslink identifications.

    • Rebecca Beveridge
    • , Johannes Stadlmann
    •  & Karl Mechtler

  • Article
    | Open Access

    Optogenetic approaches to control protein-protein interactions usually require overexpression of the target proteins. Here the authors integrate intrabodies into near-infrared- and blue-light activatable optogenetic tools to control endogenous proteins in mammalian cells.

    • Taras A. Redchuk
    • , Maksim M. Karasev
    •  & Vladislav V. Verkhusha

  • Article
    | Open Access

    Current cellular rewiring designs are typically tailored to detect single inputs. Here the authors present GEARs that function independently of engineered receptor/reporter systems and directly reroute endogenous signaling pathways to alternative genomic loci using dCas9-directed gene expression.

    • Krzysztof Krawczyk
    • , Leo Scheller
    •  & Martin Fussenegger

  • Article
    | Open Access

    Glucagon-like peptide-1 receptor is an important regulator of appetite and glucose homeostasis. Here the authors describe super-resolution microscopy and in vivo imaging compatible fluorescent probes, which reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics in islets and brain.

    • Julia Ast
    • , Anastasia Arvaniti
    •  & David J. Hodson

  • Article
    | Open Access

    Adherens junctions (AJs) mediate cell-cell adhesion between epithelial cells but tools to study their dynamic regulation are lacking. Here the authors develop an optochemical tool to stimulate the assembly of AJs through addition of a photocleavable tool and their dissociation upon exposure to light.

    • Dirk Ollech
    • , Tim Pflästerer
    •  & Elisabetta Ada Cavalcanti-Adam

  • Article
    | Open Access

    Protein AMPylation is a post-translational modification whose implications in cellular physiology are not fully understood. Here the authors develop a cell-permeable AMPylation probe and use it to identify new AMP modified proteins and investigate the role of FICD in neuronal differentiation using cerebral organoids.

    • Pavel Kielkowski
    • , Isabel Y. Buchsbaum
    •  & Stephan A. Sieber

  • Article
    | Open Access

    WNT-Frizzled (FZD) signaling plays a critical role in embryonic development, tissue homeostasis and human disease but no small molecule drugs targeting FZD with distinct efficacy have emerged so far. Here, authors identify the Smoothened agonist SAG1.3 as a partial agonist for FZD6 with limited subtype selectivity.

    • Paweł Kozielewicz
    • , Ainoleena Turku
    •  & Gunnar Schulte

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