Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using one p-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, the authors report a fungal non-ribosomal peptide synthetase PKS hybrid FnsA catalysing the formation of naringenin.

    • Hongjiao Zhang
    • , Zixin Li
    •  & Wen-Bing Yin

  • Article
    | Open Access

    Changes in glycoprotein expression are correlates of disease, but secreted glycoproteins cannot be accurately traced to their cell line of origin. Here, the authors develop a strategy to chemically tag and profile glycoproteins in a cell line-specific manner in co-culture systems and in vivo.

    • Anna Cioce
    • , Beatriz Calle
    •  & Benjamin Schumann

  • Article
    | Open Access

    Ribosomes have evolved to polymerize L-α-amino acids into proteins comprising a peptide backbone. Here, a pyridazinone backbone is formed using ribosomes in vitro, producing a variety of sequence-defined alternating block-copolymers.

    • Joongoo Lee
    • , Jaime N. Coronado
    •  & Michael C. Jewett

  • Article
    | Open Access

    Access to glycoenzymes for basic and applied research is limited by difficulties with their recombinant expression. Here, the authors describe a universal strategy for converting membrane-bound glycosyltransferases into water-soluble biocatalysts, which are expressed at high levels with retention of activity.

    • Thapakorn Jaroentomeechai
    • , Yong Hyun Kwon
    •  & Matthew P. DeLisa

  • Article
    | Open Access

    Squalene-hopene cyclase are membrane-bound enzymes used to produce bioactive compounds at industrial scale. Here, the authors show squalene-hopene cyclase spheroplasts, obtained by removing the outer cell membrane, having a higher catalytic activity than the enzymes and the whole cells, and their cross-linking for recycling and reuse.

    • Ana I. Benítez-Mateos
    • , Andreas Schneider
    •  & Francesca Paradisi

  • Article
    | Open Access

    In this manuscript the authors report accurate multi-state protein structures of the PDZ domain using biological NMR. By looking into protein structural states, the authors report an allosteric pathway at atomic resolution that validates previously reported low resolution findings and uncovered a structural hallmark of the allosteric ligand binding to the PDZ domain.

    • Dzmitry Ashkinadze
    • , Harindranath Kadavath
    •  & Roland Riek

  • Article
    | Open Access

    The nuclear pore complex (NPC) barrier is a selective phase assembled from disordered but cohesive FG domains. The authors provide a thermodynamic description of an FG phase that is ultimately simplified and yet closely recapitulates NPC transport selectivity.

    • Sheung Chun Ng
    •  & Dirk Görlich

  • Article
    | Open Access

    Ribosomally synthesized and post-translationally modified peptides are a source of antimicrobials. Here, the authors report a platform for the rapid evaluation and characterization of biosynthetic gene clusters that enables the identification of 30 structurally diverse modified peptides, including three showing antimicrobial activities.

    • Richard S. Ayikpoe
    • , Chengyou Shi
    •  & Huimin Zhao

  • Article
    | Open Access

    The development of photochromic systems is an important and growing area of research, in particular for bioactive molecular photoswitches. Here, the authors report on photopharmacological antimitotic agents, operational under visible light, based on a peptide-derived hemipiperazine photochrome.

    • Susanne Kirchner
    • , Anna-Lena Leistner
    •  & Zbigniew Pianowski

  • Article
    | Open Access

    Controlling the selectivity of the chemical modification of a genetic-manipulation-free protein is currently problematic. Here the authors report a method using cysteine-based chemoselective Linchpin Directed site-selective Modification of the lysine residue in a protein.

    • Neelesh C. Reddy
    • , Rajib Molla
    •  & Vishal Rai

  • Article
    | Open Access

    The deubiquitinase UCHL1 has been linked to cancer invasiveness and neurodegeneration yet its molecular roles have remained poorly defined. Here the authors reveal the structural basis for how UCHL1 can be specifically inhibited and how chemogenomic probes can be used to dissect its functions in living cells.

    • Christian Grethe
    • , Mirko Schmidt
    •  & Malte Gersch

  • Article
    | Open Access

    Progranulin-deficieny results in gangliosidosis due to reduced lysosomal lipids (BMP) required for ganglioside degradation. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD.

    • Sebastian Boland
    • , Sharan Swarup
    •  & Robert V. Farese Jr

  • Article
    | Open Access

    Methods to detect and distinguish the early stage of viral infection often involve complicated and time-consuming protocols. Here, the authors disclose a class of fluorescent molecules that enable fast detection of avian influenza virus infection by selectively localizing at the endoplasmic reticulum in the cell.

    • Taewon Kang
    • , Md Mamunul Haque
    •  & Dongwhan Lee

  • Article
    | Open Access

    The activity of multiple enzymes is dysregulated in cancer, but this cannot always be measured through enzyme expression. Here, the authors develop methods to measure protease activity across the organism, tissue, and single cell scales, and identify protease dysregulation in lung cancer and its response to targeted therapy.

    • Ava P. Amini
    • , Jesse D. Kirkpatrick
    •  & Sangeeta N. Bhatia

  • Article
    | Open Access

    Barley β-d-glucan glucohydrolase is a glycoside hydrolase family 3 (GH3) enzyme critical for growth and development. Here the authors carryout mutagenesis, structural analyses and multi-scale molecular dynamics to examine the binding and conformational behaviour of several β-d-glucosides during the substrate-product assisted catalysis that operates in GH3 hydrolases.

    • Sukanya Luang
    • , Xavier Fernández-Luengo
    •  & Maria Hrmova

  • Article
    | Open Access

    Genetic mutations of insulin receptor (IR) cause severe insulin resistance syndromes with no current treatment or cure. Here, the authors present that insulin-independent IR activation mechanism by peptide agonist which activate non-functional IR mutants that cause the insulin resistance syndromes.

    • Junhee Park
    • , Jie Li
    •  & Eunhee Choi

  • Article
    | Open Access

    Here, Dekkers et al. characterize associations of 1528 gut metagenomic species with the plasma metabolome in 8583 participants of the SCAPIS Study, and find that gut microbiota explain up to 58% of the variance of individual plasma metabolites.

    • Koen F. Dekkers
    • , Sergi Sayols-Baixeras
    •  & Tove Fall

  • Perspective
    | Open Access

    In this review, the authors define protein condensation diseases as conditions caused by aberrant liquid-like or solid-like states of proteins, and describe opportunities for therapeutic interventions to restore the normal phase behaviour of proteins. The review accompanies the related collection of articles published in Nature Communications focusing on possible therapeutic approaches involving liquid-liquid phase separation.

    • Michele Vendruscolo
    •  & Monika Fuxreiter

  • Article
    | Open Access

    Managing herbicide resistance problem needs the identification of new herbicidal modes of action. Here, the authors solve the crystal structures of Arabidopsis HMGR and show HMGR as a potential new herbicide target by identifying plant-specific HMGR inhibitors and engineering tolerant trait in Arabidopsis.

    • Joel Haywood
    • , Karen J. Breese
    •  & Joshua S. Mylne

  • Article
    | Open Access

    Fluorogenic detection of H2O2 in cells is established, but equivalent tools to monitor its cellular targets remain in their infancy. Here authors develop fluorogenic probes for detecting cysteine sulfenic acid, a redox modification inextricably linked to H2O2 signalling and oxidative stress.

    • Renan B. Ferreira
    • , Ling Fu
    •  & Kate S. Carroll

  • Article
    | Open Access

    Conditional Degron Tags are a valuable tool to validate and study novel therapeutic targets. Here, the authors compared 5 orthogonal tags across 16 unique proteins and provide a panel of vectors for users to systematically screen the tags with their own protein of interest.

    • Daniel P. Bondeson
    • , Zachary Mullin-Bernstein
    •  & Alessandra Ianari

  • Article
    | Open Access

    Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Δ9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries.

    • William M. Shaw
    • , Yunfeng Zhang
    •  & Tom Ellis

  • Article
    | Open Access

    Therapeutic modulation of the complement system has gained interest over the past two decades. Here, the authors provide molecular-level insight into the mode-of-action, target selectivity and species specificity of the compstatin family of complement inhibitors, which entered the clinic in 2021.

    • Christina Lamers
    • , Xiaoguang Xue
    •  & Daniel Ricklin

  • Article
    | Open Access

    The SMN protein recognizes symmetric dimethylarginine by its Tudor domain, and SMN deficiency leads to spinal muscular atrophy. Here, Liu et al. discover a small molecule that binds to the SMN Tudor domain and disrupts the interaction between SMN and RNA Polymerase II.

    • Yanli Liu
    • , Aman Iqbal
    •  & Jinrong Min

  • Article
    | Open Access

    GTP-triggered release from drug carriers has huge potential in cancer therapy but current carriers suffers from off target release due to ATP also acting as a trigger. Here, the authors report on the development of a microtubule capsule which is engineered to be responsive to only GTP not ATP and demonstrate targeted drug delivery.

    • Noriyuki Uchida
    • , Ai Kohata
    •  & Takuzo Aida

  • Article
    | Open Access

    Alpha-helix nanopores have a range of potential applications and the inclusion of non-natural amino acids allows for modification. Here, the authors report on the creation of alpha-helix pores using D-amino acids and show the pores formed, have different properties to the L-counterparts and were resistant to proteases.

    • Smrithi Krishnan R
    • , Kalyanashis Jana
    •  & Kozhinjampara R. Mahendran

  • Article
    | Open Access

    Understanding how small molecules bind to pathological aggregates is of importance for therapeutic and diagnostic development in diseases such as Parkinson’s Disease. Here, the authors reveal a binding site of anle138b to lipid-induced α-synuclein fibrils.

    • Leif Antonschmidt
    • , Dirk Matthes
    •  & Loren B. Andreas

  • Article
    | Open Access

    The transfer of electronic energy through a photosystem can harm the photosynthetic apparatus when not balanced with CO2 fixation. Here, the authors show that CO2 modulates electronic energy transfer in cyanobacteria by binding to and enhancing the activity of the light-harvesting complex.

    • Alejandra Guillén-García
    • , Savannah E. R. Gibson
    •  & Martin J. Cann

  • Article
    | Open Access

    Efficient engineering of enzymes for expanded substrate scope is currently challenging. Here, the authors develop simple principles of how to design and interpret Substrate Multiplexed Screening assays to guide protein engineering to enable activity improvements with simultaneously with multiple substrates.

    • Allwin D. McDonald
    • , Peyton M. Higgins
    •  & Andrew R. Buller

  • Article
    | Open Access

    A challenge for synthetic biology is the design and construction of prototissue. Here, the authors spatially segregate layers of enzyme-decorated coacervate protocells as a model prototissue capable of chemical signal processing and modulating outputs of nitric oxide to inhibit blood clot formation.

    • Songyang Liu
    • , Yanwen Zhang
    •  & Jianbo Liu

  • Article
    | Open Access

    Establishing methods to access the chemical space that lies beyond canonical terpenoid biosynthesis will increase the applications of isoprenoids. Here, the authors reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones by engineered yeast and synthesize 28 different unique terpenes.

    • Codruta Ignea
    • , Morten H. Raadam
    •  & Sotirios C. Kampranis

  • Article
    | Open Access

    Researchers have been trying to mimick the cellular spatiotemporal control in normal cells with different approaches. Here, the authors present semi-permeable polymersomes comprising of amphiphilic triblock copolymers to achieve external signal-driven complex coacervation and biophysical reconstitution of cytoskeleton.

    • Hanjin Seo
    •  & Hyomin Lee

  • Article
    | Open Access

    The chemical diversity of peptides from ribosomal origin is a growing field of research. Here, the authors report the discovery, genomic and biosynthetic investigations of kintamdin, a ribosomally synthesized and post-translationally modified peptides featuring a beta-enamino acid and a bis-thioether macrocyclic motif.

    • Shan Wang
    • , Sixing Lin
    •  & Hai Deng

  • Article
    | Open Access

    Methods for fluorescently labelling DNAs are expensive and labour-intensive. Here the authors report an in situ DNA labelling strategy for oligonucleotides as well as dsDNA that makes use of aldehyde-reactive rotor dyes to trap AP sites resulting from excision of deaminated DNA bases.

    • Yong Woong Jun
    • , Emily M. Harcourt
    •  & Eric T. Kool

  • Article
    | Open Access

    Engineering enzymes to utilize the noncanonical redox cofactors such as nicotinamide mononucleotide (NMN + ) is challenging. Here, the authors report a growth-based selection platform for NMN + -reducing enzyme engineering and show its application in developing a phosphite dehydrogenase with improved catalytic efficiency.

    • Linyue Zhang
    • , Edward King
    •  & Han Li

  • Article
    | Open Access

    The development of antimalarials against the human liver and asexual blood stages is one of the top public health challenges. Here, the authors report a single-step biochemical assay for the characterization of prolyl-tRNA synthetase inhibitors, and develop high-affinity inhibitors for the enzyme, including elusive triple-site ligands.

    • Mark A. Tye
    • , N. Connor Payne
    •  & Ralph Mazitschek

  • Article
    | Open Access

    How triptonide is made in the medicinal plant Tripterygium wilfordii is largely unknown. Here, the authors report the identification and characterization of a suite of cytochrome P450s and show their function in catalyzing the formation of triptonide from miltriadiene in tobacco and baker’s yeast.

    • Nikolaj Lervad Hansen
    • , Louise Kjaerulff
    •  & Johan Andersen-Ranberg

  • Article
    | Open Access

    Engineering peptide assembly that controls integrin ligand presentation on the molecular level possesses by far the highest ligand density, expanding the perspective of ligand-density-dependent modulation.

    • Xunwu Hu
    • , Sona Rani Roy
    •  & Ye Zhang

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