Enzymes articles within Nature Communications

Featured

  • Article
    | Open Access

    Solar-driven artificial food synthesis from CO2 provides an approach to overcome the limitations of natural photosynthesis, but it is very challenging. Here, the authors report a hybrid electrocatalytic-biocatalytic flow system, coupling photovoltaics-powered electrocatalysis (CO2 to formate) with a five enzyme cascade platform (formate to sugar), which achieves conversion of CO2 to C6 sugar (L-sorbose) with a solar-to-food energy conversion efficiency of 3.5%.

    • Guangyu Liu
    • , Yuan Zhong
    •  & Yujie Xiong
  • Article
    | Open Access

    Diels-Alderases (DAs), enzymes catalyzing [4 + 2] cycloaddition reactions, are of high interest, but insights into their evolution are lacking. Here, the authors investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites, suggesting they evolved from an ancestor functioning as a flavin adenine dinucleotide-dependent oxidocyclase.

    • Qi Ding
    • , Nianxin Guo
    •  & Xiaoguang Lei
  • Article
    | Open Access

    The pathogen Legionella pneumophila mediates NAD+-dependent ubiquitination pathways upon infection. Here, the authors show the Legionella effector MavL reverses ubiquitin ADP-ribosylation to regulate these pathways. MavL represents a new macrodomain class specific for reversal of arginine ADP-ribosylation with distinct ADP-ribose binding features.

    • Zhengrui Zhang
    • , Jiaqi Fu
    •  & Chittaranjan Das
  • Article
    | Open Access

    Designing complex synthetic materials for enzyme immobilization could unlock the utility of biocatalysis in extreme environments. Here, the authors report on random copolymer brushes as dynamic immobilization supports that enable supra-biological catalytic performance of immobilized enzymes.

    • Héctor Sánchez-Morán
    • , Joel L. Kaar
    •  & Daniel K. Schwartz
  • Article
    | Open Access

    The authors previously showed that a histidine nucleophile and a flexible arginine can work in synergy to accelerate the Morita Baylis-Hillman (MBH) reaction. Here, they report another efficient MBHase that employs a non-canonical Nδ-methylhistidine nucleophile paired with a catalytic glutamate, providing an alternative mechanistic solution for MBH catalysis.

    • Amy E. Hutton
    • , Jake Foster
    •  & Anthony P. Green
  • Article
    | Open Access

    Understanding the complex relationships between enzyme sequence, folding stability and catalytic activity is essential for applications, but current technologies cannot simultaneously resolve both stability and activity phenotypes and couple these to gene sequences at large scale. Here, the authors report Enzyme Proximity Sequencing (EP-Seq), a deep mutational scanning method to assay both expression level and catalytic activity of thousands of oxidoreductase variants from a cellular pool in a single experiment.

    • Rosario Vanella
    • , Christoph Küng
    •  & Michael A. Nash
  • Article
    | Open Access

    Circulating monocytes contribute to the transition to pain chronicity but the molecular events that cause their deployment are still unclear. Using a mouse model of hyperalgesic priming, here the authors show that blood monocytes contribute to the emergence of chronic pain via a mechanism that requires a transient disruption of NAAA-regulated lipid signaling.

    • Yannick Fotio
    • , Alex Mabou Tagne
    •  & Daniele Piomelli
  • Article
    | Open Access

    Poly-γ-glutamate tails are a distinctive feature of folate and F420 cofactors, but it was unclear how these tails elongate while maintaining substrate specificity. Here, the authors discover that folylpolyglutamate synthase and γ-glutamyl ligase enzymes add successive L-glutamates to the termini of the growing γ-glutamyl chain in a processive mechanism.

    • Ghader Bashiri
    • , Esther M. M. Bulloch
    •  & Christopher J. Squire
  • Article
    | Open Access

    Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

    • Elizabeth L. Bell
    • , Gloria Rosetto
    •  & Gregg T. Beckham
  • 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

    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

    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

    Here, the authors perform statistical analyses to demonstrate that epistasis is highly pervasive in adaptive evolutionary trajectories of enzymes. Using epistatic data, they expose higher-order rewiring of intramolecular amino acid networks.

    • Karol Buda
    • , Charlotte M. Miton
    •  & Nobuhiko Tokuriki
  • Article
    | Open Access

    Botulinum neurotoxins (BoNTs), the causative agents of the disease botulism, are potent biological toxins. Here the authors use Designed Ankyrin Repeat Proteins (DARPins) to probe BoNT structure and function: DARPin-F5 that completely blocks SNAP25 substrate cleavage by BoNT/A1 in vitro was identified.

    • Oneda Leka
    • , Yufan Wu
    •  & Richard A. Kammerer
  • Article
    | Open Access

    The NLRP3 inflammasome is activated in two steps, priming and assembly, in response to endogenous, microbial, and other environmental danger signals. Here authors show that the assembly step is regulated by acetylation, and inhibition of this post-translational modification prevents full activation of the inflammasome.

    • Yening Zhang
    • , Ling Luo
    •  & Kai Zhao
  • Article
    | Open Access

    Developmental defects in left-right cardiac determination in humans are associated with ciliary dysfunction and low airway epithelial nitric oxide production. Here, the authors show that cytoglobin is essential for nitric oxide signaling, cilia function, and left-right patterning during zebrafish development.

    • Elizabeth R. Rochon
    • , Jianmin Xue
    •  & Paola Corti
  • 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

    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

    NanoLuc luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Here the authors use, protein crystal structures and biochemical analyses to provide an atomistic description of its catalytic mechanism and allosteric behaviour.

    • Michal Nemergut
    • , Daniel Pluskal
    •  & Martin Marek
  • Article
    | Open Access

    Functional annotation of open reading frames in microbial genomes remains substantially incomplete. Here, Kim et al. present a deep learning model that utilizes transformer layers as a neural network architecture to predict specific catalytic functions for enzyme-encoding genes of unknown function.

    • Gi Bae Kim
    • , Ji Yeon Kim
    •  & Sang Yup Lee
  • Article
    | Open Access

    Many AAA+ (ATPases associated with diverse cellular activities) proteins function as a hexamer to remodel protein substrates. Here, the authors report the discovery of a pentameric form of the Lon AAA+ protease and show that it plays a role in the substrate-dependent activation of the AAA+ protein.

    • Shanshan Li
    • , Kan-Yen Hsieh
    •  & Chung-I Chang
  • Article
    | Open Access

    Biological degradation of glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, the authors report an O-glycoside β-eliminase from Agrobacterium tumefaciens that converts the C3-oxidized O-β-d-glucoside of phloretin into the aglycone and the 2-hydroxy-3-keto-d-glycal elimination product, and suggest convergent evolution of β-eliminase active sites for the cleavage of natural product 3-keto-O-glycosides.

    • Johannes Bitter
    • , Martin Pfeiffer
    •  & Bernd Nidetzky
  • 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

    In this work, Bay et al describe the construction of the first genome-scale metabolic model for the parasitic whipworm, Trichuris muris and use it to identify novel metabolic pathways and predict critical enzymes and essential metabolites for worm survival.

    • Ömer F. Bay
    • , Kelly S. Hayes
    •  & Ian S. Roberts
  • Article
    | Open Access

    Hollow inorganic spheres (HISs) hold potential in various technological areas including biocatalysis and biomedicine, but the harsh synthetic conditions have precluded the use of HISs in biological fields. Here, the authors report a biocompatible strategy for synthesizing metal hydroxide HISs that can function as tandem-biocatalytic reactors.

    • Sang Yeong Han
    • , Nayoung Kim
    •  & Insung S. Choi
  • Article
    | Open Access

    Currently the structure and biological function of Lactate Dehydrogenase D (LDHD) are unclear. Here the authors report the structure of LDHD bound with various ligands and show that LDHD is a general dehydrogenase for D-2-hydroxyacids with small to moderate-size hydrophobic moieties and investigate loss-of-function mutations that play an important role in D-lactic acidosis.

    • Shan Jin
    • , Xingchen Chen
    •  & Jianping Ding
  • Article
    | Open Access

    The bacterium Listeria monocytogenes possesses two major virulence factors, broad-range phospholipase C (LmPC-PLC) and the pore-forming toxin listeriolysin O (LLO). Here, authors perform structural and biochemical analysis of LmPC-PLC and show that unique structural features enable self-regulation of its enzymatic activity and positive synergy with the pore-forming toxin listeriolysin O.

    • Nejc Petrišič
    • , Maksimiljan Adamek
    •  & Marjetka Podobnik
  • 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

    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

    Lysine acetylation is highly prevalent in metabolic enzymes. Here, the authors highlight the diverse roles of acetylation and show that G6PD acetylation can activate/deactivate G6PD, and promote G6PD ubiquitylation and phosphorylation, its interaction with p53, and p53-dependent pro-apoptotic events.

    • Fang Wu
    • , Natali H. Muskat
    •  & Eyal Arbely
  • Article
    | Open Access

    Dermatitis herpetiformis, a skin manifestation of the gluten-sensitive condition celiac disease, is hallmarked by autoantibody production to transglutaminase 3. Here, the authors present the 3D-structures of an autoantibody bound to transglutaminase 3 with an inhibitor mimicking a gluten-peptide substrate.

    • Julie Elisabeth Heggelund
    • , Saykat Das
    •  & Ludvig M. Sollid
  • 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

    Currently little is known about the acetylation on sugar moieties. Here the authors report a saponin acetyltransferase from Astragalus membranaceus, AmAT7-3, and utilise crystal structures and QM/MM computation to elucidate the catalytic mechanism: they generate mutants for specific site acetylation.

    • Linlin Wang
    • , Zhihui Jiang
    •  & Xue Qiao