Articles

  • Article |

    Biocatalytic cascade reactions using engineered variants of ferulic acid decarboxylase coupled to carboxylic acid reductase utilize carbon dioxide fixation to enable the carboxylation and functionalization of styrene and other aromatic compounds.

    • Godwin A. Aleku
    • , Annica Saaret
    • , Ruth T. Bradshaw-Allen
    • , Sasha R. Derrington
    • , Gabriel R. Titchiner
    • , Irina Gostimskaya
    • , Deepankar Gahloth
    • , David A. Parker
    • , Sam Hay
    •  & David Leys
  • Article |

    A robust mass spectrometry workflow was developed for rapid drug perturbation profiling in multiple cell lines, enabling improved mechanistic deconvolution of single compounds and revealing novel mechanisms of action.

    • Benjamin Ruprecht
    • , Julie Di Bernardo
    • , Zhao Wang
    • , Xuan Mo
    • , Oleg Ursu
    • , Matthew Christopher
    • , Rafael B. Fernandez
    • , Li Zheng
    • , Brian D. Dill
    • , Huijun Wang
    • , Yuting Xu
    • , Andy Liaw
    • , Jonathan D. Mortison
    • , Nirodhini Siriwardana
    • , Brian Andresen
    • , Meir Glick
    • , James R. Tata
    • , Victoria Kutilek
    • , Ivan Cornella-Taracido
    •  & An Chi
  • Article |

    Highly selective activators of IRE1/XBP1 splicing pathway were identified via high-throughput screen, which promoted the degradation of APP and reduced APP-associated mitochondrial toxicity in an IRE1-dependent manner.

    • Julia M. D. Grandjean
    • , Aparajita Madhavan
    • , Lauren Cech
    • , Bryan O. Seguinot
    • , Ryan J. Paxman
    • , Emery Smith
    • , Louis Scampavia
    • , Evan T. Powers
    • , Christina B. Cooley
    • , Lars Plate
    • , Timothy P. Spicer
    • , Jeffery W. Kelly
    •  & R. Luke Wiseman
  • Article |

    TH1760 is a first-in-class, potent, selective and cell-active inhibitor against human NUDT15, which sensitizes cells to 6-thioguanine treatment. TH1760 represents a valuable tool for deciphering the enigmatic functions of NUDT15.

    • Si Min Zhang
    • , Matthieu Desroses
    • , Anna Hagenkort
    • , Nicholas C. K. Valerie
    • , Daniel Rehling
    • , Megan Carter
    • , Olov Wallner
    • , Tobias Koolmeister
    • , Adam Throup
    • , Ann-Sofie Jemth
    • , Ingrid Almlöf
    • , Olga Loseva
    • , Thomas Lundbäck
    • , Hanna Axelsson
    • , Shruti Regmi
    • , Antonio Sarno
    • , Andreas Krämer
    • , Linda Pudelko
    • , Lars Bräutigam
    • , Azita Rasti
    • , Mona Göttmann
    • , Elisée Wiita
    • , Juliane Kutzner
    • , Torsten Schaller
    • , Christina Kalderén
    • , Armando Cázares-Körner
    • , Brent D. G. Page
    • , Rosa Krimpenfort
    • , Saeed Eshtad
    • , Mikael Altun
    • , Sean G. Rudd
    • , Stefan Knapp
    • , Martin Scobie
    • , Evert J. Homan
    • , Ulrika Warpman Berglund
    • , Pål Stenmark
    •  & Thomas Helleday
  • Article |

    A new ligand against the GPCR GLP-1R acts as a positive allosteric modulator, binding both the receptor and the orthosteric ligand, accessing the peptide ligand within the interface between transmembrane domains 1 and 2 of the receptor.

    • Ana B. Bueno
    • , Bingfa Sun
    • , Francis S. Willard
    • , Dan Feng
    • , Joseph D. Ho
    • , David B. Wainscott
    • , Aaron D. Showalter
    • , Michal Vieth
    • , Qi Chen
    • , Cynthia Stutsman
    • , Betty Chau
    • , James Ficorilli
    • , Francisco J. Agejas
    • , Graham R. Cumming
    • , Alma Jiménez
    • , Isabel Rojo
    • , Tong Sun Kobilka
    • , Brian K. Kobilka
    •  & Kyle W. Sloop
  • Article |

    An econometric model built on regulatory networks and calibrated by proteomics data identifies nonessential transcription factors that when deleted in Escherichia coli result in a strain with an expanded proteome for engineering applications.

    • Gustavo Lastiri-Pancardo
    • , Jonathan S. Mercado-Hernández
    • , Juhyun Kim
    • , José I. Jiménez
    •  & José Utrilla
  • Article |

    Engineering cleavage sites into gas vesicle proteins enables protease-responsive regulation of gas vesicle mechanics and activates them as ultrasound contrast agents for imaging applications in cells and living mice.

    • Anupama Lakshmanan
    • , Zhiyang Jin
    • , Suchita P. Nety
    • , Daniel P. Sawyer
    • , Audrey Lee-Gosselin
    • , Dina Malounda
    • , Mararet B. Swift
    • , David Maresca
    •  & Mikhail G. Shapiro
  • Article |

    A synthetic phase separation system consisting of two protein components with tunable parameters was developed to visualize and characterize phase diagrams in living cells, revealing that increasing the interaction affinity enhances phase separation and the viscosity of condensates in vivo.

    • Meta Heidenreich
    • , Joseph M. Georgeson
    • , Emanuele Locatelli
    • , Lorenzo Rovigatti
    • , Saroj Kumar Nandi
    • , Avital Steinberg
    • , Yotam Nadav
    • , Eyal Shimoni
    • , Samuel A. Safran
    • , Jonathan P. K. Doye
    •  & Emmanuel D. Levy
  • Article |

    Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.

    • Lisa J. Clark
    • , James Krieger
    • , Alex D. White
    • , Vasyl Bondarenko
    • , Saifei Lei
    • , Fei Fang
    • , Ji Young Lee
    • , Pemra Doruker
    • , Thore Böttke
    • , Frederic Jean-Alphonse
    • , Pei Tang
    • , Thomas J. Gardella
    • , Kunhong Xiao
    • , Ieva Sutkeviciute
    • , Irene Coin
    • , Ivet Bahar
    •  & Jean-Pierre Vilardaga
  • Article |

    Structural, conformational and biochemical characterization of the AROM complex and its constituent shikimate pathway domains reveals how the complex balances compactness and conformational freedom, yet does not benefit from substrate channeling.

    • Harshul Arora Verasztó
    • , Maria Logotheti
    • , Reinhard Albrecht
    • , Alexander Leitner
    • , Hongbo Zhu
    •  & Marcus D. Hartmann
  • Article |

    Utilization of structural proteins with intrinsically disordered regions enables the formation of membraneless organelles in Escherichia coli through liquid–liquid phase separation, as well as their functionalization with active enzymes.

    • Shao-Peng Wei
    • , Zhi-Gang Qian
    • , Chun-Fei Hu
    • , Fang Pan
    • , Meng-Ting Chen
    • , Sang Yup Lee
    •  & Xiao-Xia Xia
  • Article |

    Structural and biochemical analysis reveal that tetracenomycin X acts as an inhibitor of protein synthesis by binding within the exit tunnel in a large ribosomal unit to prevent the prolongation of the nascent polypeptide chain.

    • Ilya A. Osterman
    • , Maximiliane Wieland
    • , Tinashe P. Maviza
    • , Kseniya A. Lashkevich
    • , Dmitrii A. Lukianov
    • , Ekaterina S. Komarova
    • , Yuliya V. Zakalyukina
    • , Robert Buschauer
    • , Dmitrii I. Shiriaev
    • , Semen A. Leyn
    • , Jaime E. Zlamal
    • , Mikhail V. Biryukov
    • , Dmitry A. Skvortsov
    • , Vadim N. Tashlitsky
    • , Vladimir I. Polshakov
    • , Jingdong Cheng
    • , Yury S. Polikanov
    • , Alexey A. Bogdanov
    • , Andrei L. Osterman
    • , Sergey E. Dmitriev
    • , Roland Beckmann
    • , Olga A. Dontsova
    • , Daniel N. Wilson
    •  & Petr V. Sergiev
  • Article |

    BotH is an unusual α/β-hydrolase-fold enzyme that catalyzes epimerization of an aspartate residue during bottromycin biosynthesis via a mechanism distinct from other known peptide natural product epimerases.

    • Asfandyar Sikandar
    • , Laura Franz
    • , Sebastian Adam
    • , Javier Santos-Aberturas
    • , Liliya Horbal
    • , Andriy Luzhetskyy
    • , Andrew W. Truman
    • , Olga V. Kalinina
    •  & Jesko Koehnke
  • Article |

    A Raman-based imaging approach that can distinguish closely related chemical species used to characterize the distribution of lipids throughout the body of intact Caenorhabditis elegans worms shows that the epidermis is an important fat-storage reservoir.

    • Wei-Wen Chen
    • , George A. Lemieux
    • , Charles H. Camp Jr
    • , Ta-Chau Chang
    • , Kaveh Ashrafi
    •  & Marcus T. Cicerone
  • Article |

    Manumycin natural products were found to target the E3 ligase UBR7 and engage in molecular glue interactions with p53, leading to the activation of p53 and cell death.

    • Yosuke Isobe
    • , Mikiko Okumura
    • , Lynn M. McGregor
    • , Scott M. Brittain
    • , Michael D. Jones
    • , Xiaoyou Liang
    • , Ross White
    • , William Forrester
    • , Jeffrey M. McKenna
    • , John A. Tallarico
    • , Markus Schirle
    • , Thomas J. Maimone
    •  & Daniel K. Nomura
  • Article |

    A structural and biochemical study of bacterial β-barrel assembly machinery component BamA with transport substrate RcsF shows an inward-open conformation with RcsF trapped inside the β-barrel lumen and suggests a push–pull substrate export mechanism.

    • Raquel Rodríguez-Alonso
    • , Juliette Létoquart
    • , Van Son Nguyen
    • , Gwennaelle Louis
    • , Antonio N. Calabrese
    • , Bogdan I. Iorga
    • , Sheena E. Radford
    • , Seung-Hyun Cho
    • , Han Remaut
    •  & Jean-François Collet
  • Article |

    The iPROBE platform accelerates the design and optimization of engineered biosynthetic pathways using a combination of cell-free protein synthesis, in vitro pathway assembly and a scoring system to identify high-performing combinations.

    • Ashty S. Karim
    • , Quentin M. Dudley
    • , Alex Juminaga
    • , Yongbo Yuan
    • , Samantha A. Crowe
    • , Jacob T. Heggestad
    • , Shivani Garg
    • , Tanus Abdalla
    • , William S. Grubbe
    • , Blake J. Rasor
    • , David N. Coar
    • , Maria Torculas
    • , Michael Krein
    • , FungMin (Eric) Liew
    • , Amy Quattlebaum
    • , Rasmus O. Jensen
    • , Jeffrey A. Stuart
    • , Sean D. Simpson
    • , Michael Köpke
    •  & Michael C. Jewett
  • Article |

    Single-molecule and super-resolution approaches define a monomer–dimer equilibrium of µ-opioid receptors and show that receptors form agonist-induced dimers coincident with β-arrestin2 binding to receptors.

    • Jan Möller
    • , Ali Isbilir
    • , Titiwat Sungkaworn
    • , Brendan Osberg
    • , Christos Karathanasis
    • , Vikram Sunkara
    • , Eugene O. Grushevskyi
    • , Andreas Bock
    • , Paolo Annibale
    • , Mike Heilemann
    • , Christof Schütte
    •  & Martin J. Lohse
  • Article |

    A 19F-NMR-based method monitoring the conformational dynamics of the glutamate transporter GltPh identified one inward- and two outward-facing states, including one unanticipated outward-facing state that was characterized by cryo-EM.

    • Yun Huang
    • , Xiaoyu Wang
    • , Guohua Lv
    • , Asghar M. Razavi
    • , Gerard H. M. Huysmans
    • , Harel Weinstein
    • , Clay Bracken
    • , David Eliezer
    •  & Olga Boudker
  • Article |

    Activity-based protein profiling (ABPP) was used to identify and optimize bioactive, selective pharmacological enzyme activators of the serine hydrolase LYPLAL1, which improved the metabolic defects of diet-induced obese mice.

    • Bernard P. Kok
    • , Srijana Ghimire
    • , Woojoo Kim
    • , Shreyosree Chatterjee
    • , Tyler Johns
    • , Seiya Kitamura
    • , Jerome Eberhardt
    • , Daisuke Ogasawara
    • , Janice Xu
    • , Ara Sukiasyan
    • , Sean M. Kim
    • , Cristina Godio
    • , Julia M. Bittencourt
    • , Michael Cameron
    • , Andrea Galmozzi
    • , Stefano Forli
    • , Dennis W. Wolan
    • , Benjamin F. Cravatt
    • , Dale L. Boger
    •  & Enrique Saez
  • Article |

    A negative allosteric modulator of the G-protein-coupled receptor β2-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch conformation.

    • Xiangyu Liu
    • , Jonas Kaindl
    • , Magdalena Korczynska
    • , Anne Stößel
    • , Daniela Dengler
    • , Markus Stanek
    • , Harald Hübner
    • , Mary J. Clark
    • , Jake Mahoney
    • , Rachel Ann Matt
    • , Xinyu Xu
    • , Kunio Hirata
    • , Brian K. Shoichet
    • , Roger K. Sunahara
    • , Brian K. Kobilka
    •  & Peter Gmeiner
  • Article |

    Cellular glycosylation facilitates molecular recognition of cells and biomolecules. A two-step N-glycan editing method enables selective glycoform ‘deletion’ and ‘insertion’ of new glycans, which can be used to probe their biological functions.

    • Feng Tang
    • , Mang Zhou
    • , Ken Qin
    • , Wei Shi
    • , Ansor Yashinov
    • , Yang Yang
    • , Liyun Yang
    • , Dongliang Guan
    • , Lei Zhao
    • , Yubo Tang
    • , Yujie Chang
    • , Lifen Zhao
    • , Huaiyu Yang
    • , Hu Zhou
    • , Ruimin Huang
    •  & Wei Huang
  • Article |

    Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several nucleoside antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.

    • Zheng Cui
    • , Jonathan Overbay
    • , Xiachang Wang
    • , Xiaodong Liu
    • , Yinan Zhang
    • , Minakshi Bhardwaj
    • , Anke Lemke
    • , Daniel Wiegmann
    • , Giuliana Niro
    • , Jon S. Thorson
    • , Christian Ducho
    •  & Steven G. Van Lanen
  • Article |

    A highly selective covalent peptide inhibitor of the peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is used to show that Pin1 cooperates with mutant KRAS to promote pancreatic ductal adenocarcinoma (PDAC) transformation.

    • Benika J. Pinch
    • , Zainab M. Doctor
    • , Behnam Nabet
    • , Christopher M. Browne
    • , Hyuk-Soo Seo
    • , Mikaela L. Mohardt
    • , Shingo Kozono
    • , Xiaolan Lian
    • , Theresa D. Manz
    • , Yujin Chun
    • , Shin Kibe
    • , Daniel Zaidman
    • , Dina Daitchman
    • , Zoe C. Yeoh
    • , Nicholas E. Vangos
    • , Ezekiel A. Geffken
    • , Li Tan
    • , Scott B. Ficarro
    • , Nir London
    • , Jarrod A. Marto
    • , Stephen Buratowski
    • , Sirano Dhe-Paganon
    • , Xiao Zhen Zhou
    • , Kun Ping Lu
    •  & Nathanael S. Gray
  • Article |

    Prostaglandins PGE1 and PGA1 have neuroprotective effects by enhancing the transcriptional activity of Nurr1 by directly binding to its ligand-binding domain and upregulating their target genes implicated in Parkinson’s disease.

    • Sreekanth Rajan
    • , Yongwoo Jang
    • , Chun-Hyung Kim
    • , Woori Kim
    • , Hui Ting Toh
    • , Jeha Jeon
    • , Bin Song
    • , Aida Serra
    • , Julien Lescar
    • , Jun Yeob Yoo
    • , Serap Beldar
    • , Hong Ye
    • , Congbao Kang
    • , Xue-Wei Liu
    • , Melissa Feitosa
    • , Yeahan Kim
    • , Dabin Hwang
    • , Geraldine Goh
    • , Kah-Leong Lim
    • , Hye Min Park
    • , Choong Hwan Lee
    • , Sungwhan F. Oh
    • , Gregory A. Petsko
    • , Ho Sup Yoon
    •  & Kwang-Soo Kim
  • Article |

    Imaging studies revealed that m6A-binding YTHDF proteins promoted phase separation of core proteins of stress granules by reducing the critical size and activation energy barrier, thus promoting the formation of stress granules in cells.

    • Ye Fu
    •  & Xiaowei Zhuang
  • Article |

    Comprehensive informatic, structural and biochemical characterization of the GH128 family defines subgroups of glycoside hydrolase enzymes with unique recognition and cleavage mechanisms for 1,3-beta-glucan polysaccharide substrates.

    • Camila R. Santos
    • , Pedro A. C. R. Costa
    • , Plínio S. Vieira
    • , Sinkler E. T. Gonzalez
    • , Thamy L. R. Correa
    • , Evandro A. Lima
    • , Fernanda Mandelli
    • , Renan A. S. Pirolla
    • , Mariane N. Domingues
    • , Lucelia Cabral
    • , Marcele P. Martins
    • , Rosa L. Cordeiro
    • , Atílio T. Junior
    • , Beatriz P. Souza
    • , Érica T. Prates
    • , Fabio C. Gozzo
    • , Gabriela F. Persinoti
    • , Munir S. Skaf
    •  & Mario T. Murakami
  • Article |

    Engineering of yeast transcription factors and design of hybrid DNA promoter elements have resulted in a toolkit for tunable and orthogonal regulation of gene expression in Arabidopsis thaliana and Nicotiana benthamiana plants.

    • Michael S. Belcher
    • , Khanh M. Vuu
    • , Andy Zhou
    • , Nasim Mansoori
    • , Amanda Agosto Ramos
    • , Mitchell G. Thompson
    • , Henrik V. Scheller
    • , Dominique Loqué
    •  & Patrick M. Shih
  • Article |

    Biosensors of guanine exchange factors (GEFs) and red-shifted GTPase biosensors are used to visualize GEF and GTPase activities in the same cells and enable correlation analysis to reveal which GEF–GTPase interactions regulate cell movement.

    • Daniel J. Marston
    • , Marco Vilela
    • , Jaewon Huh
    • , Jinqi Ren
    • , Mihai L. Azoitei
    • , George Glekas
    • , Gaudenz Danuser
    • , John Sondek
    •  & Klaus M. Hahn
  • Article |

    Evolution of a group of plant cellulose synthase-like enzymes into specialized glycosyltransferases in the endoplasmic reticulum membrane confers the ability to glucuronidate triterpenoid saponins and other specialized metabolites.

    • Adam Jozwiak
    • , Prashant D. Sonawane
    • , Sayantan Panda
    • , Constantine Garagounis
    • , Kalliope K. Papadopoulou
    • , Bekele Abebie
    • , Hassan Massalha
    • , Efrat Almekias-Siegl
    • , Tali Scherf
    •  & Asaph Aharoni
  • Article |

    Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.

    • Jonathan M. Ghergurovich
    • , Juan C. García-Cañaveras
    • , Joshua Wang
    • , Emily Schmidt
    • , Zhaoyue Zhang
    • , Tara TeSlaa
    • , Harshel Patel
    • , Li Chen
    • , Emily C. Britt
    • , Marta Piqueras-Nebot
    • , Mari Carmen Gomez-Cabrera
    • , Agustín Lahoz
    • , Jing Fan
    • , Ulf H. Beier
    • , Hahn Kim
    •  & Joshua D. Rabinowitz
  • Article |

    Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity

    • Nathaniel C. Gilbert
    • , Jana Gerstmeier
    • , Erin E. Schexnaydre
    • , Friedemann Börner
    • , Ulrike Garscha
    • , David B. Neau
    • , Oliver Werz
    •  & Marcia E. Newcomer
  • Article |

    An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.

    • Elliot D. Mock
    • , Mohammed Mustafa
    • , Ozge Gunduz-Cinar
    • , Resat Cinar
    • , Gavin N. Petrie
    • , Vasudev Kantae
    • , Xinyu Di
    • , Daisuke Ogasawara
    • , Zoltan V. Varga
    • , Janos Paloczi
    • , Cristina Miliano
    • , Giulia Donvito
    • , Annelot C. M. van Esbroeck
    • , Anouk M. F. van der Gracht
    • , Ioli Kotsogianni
    • , Joshua K. Park
    • , Andrea Martella
    • , Tom van der Wel
    • , Marjolein Soethoudt
    • , Ming Jiang
    • , Tiemen J. Wendel
    • , Antonius P. A. Janssen
    • , Alexander T. Bakker
    • , Colleen M. Donovan
    • , Laura I. Castillo
    • , Bogdan I. Florea
    • , Jesse Wat
    • , Helma van den Hurk
    • , Matthias Wittwer
    • , Uwe Grether
    • , Andrew Holmes
    • , Constant A. A. van Boeckel
    • , Thomas Hankemeier
    • , Benjamin F. Cravatt
    • , Matthew W. Buczynski
    • , Matthew N. Hill
    • , Pal Pacher
    • , Aron H. Lichtman
    •  & Mario van der Stelt
  • Article |

    Structural and smFRET analysis reveals the mechanism of opposing catalytic activities of bifunctional Rel enzymes; that is, activation of one of the catalytic domains leads to allosteric inactivation of the other.

    • Hedvig Tamman
    • , Katleen Van Nerom
    • , Hiraku Takada
    • , Niels Vandenberk
    • , Daniel Scholl
    • , Yury Polikanov
    • , Johan Hofkens
    • , Ariel Talavera
    • , Vasili Hauryliuk
    • , Jelle Hendrix
    •  & Abel Garcia-Pino
  • Article |

    Development of BRET sensors for nearly all major G proteins show that GPCR–G-protein coupling ranges from promiscuous to extremely specific, Switch III is a novel site for G-protein engineering, and optimal donor–acceptor positioning is non-obvious.

    • Reid H. J. Olsen
    • , Jeffrey F. DiBerto
    • , Justin G. English
    • , Alexis M. Glaudin
    • , Brian E. Krumm
    • , Samuel T. Slocum
    • , Tao Che
    • , Ariana C. Gavin
    • , John D. McCorvy
    • , Bryan L. Roth
    •  & Ryan T. Strachan
  • Article |

    Lipidomics across the bilayer membrane plus biophysical and fluorescence approaches find asymmetry in phospholipid unsaturation and localization of protein transmembrane domains based on their ability to pack within the different membrane leaflets.

    • J. H. Lorent
    • , K. R. Levental
    • , L. Ganesan
    • , G. Rivera-Longsworth
    • , E. Sezgin
    • , M. Doktorova
    • , E. Lyman
    •  & I. Levental
  • Article |

    Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension.

    • Danyao Du
    • , Yohei Katsuyama
    • , Masanobu Horiuchi
    • , Shinya Fushinobu
    • , Aochiu Chen
    • , Tony D. Davis
    • , Michael D. Burkart
    •  & Yasuo Ohnishi
  • Article |

    The authors developed a metabolic labeling method via incorporation of allyl-SAM analogs to profile transcriptome-wide m6A at base resolution, which enables identification of m6A motifs and clustered m6A sites.

    • Xiao Shu
    • , Jie Cao
    • , Mohan Cheng
    • , Siying Xiang
    • , Minsong Gao
    • , Ting Li
    • , Xiner Ying
    • , Fengqin Wang
    • , Yanan Yue
    • , Zhike Lu
    • , Qing Dai
    • , Xiaolong Cui
    • , Lijia Ma
    • , Yizhen Wang
    • , Chuan He
    • , Xinhua Feng
    •  & Jianzhao Liu
  • Article |

    Domain insertion into the loop region of AcrIIC1 leads to a variant with enhanced inhibitory activity toward Neisseria meningitides Cas9, while structure-guided design turns AcrIIC1 into a potent inhibitor of Staphylococcus aureus Cas9.

    • Jan Mathony
    • , Zander Harteveld
    • , Carolin Schmelas
    • , Julius Upmeier zu Belzen
    • , Sabine Aschenbrenner
    • , Wei Sun
    • , Mareike D. Hoffmann
    • , Christina Stengl
    • , Andreas Scheck
    • , Sandrine Georgeon
    • , Stéphane Rosset
    • , Yanli Wang
    • , Dirk Grimm
    • , Roland Eils
    • , Bruno E. Correia
    •  & Dominik Niopek
  • Article |

    In plants, the cytosolic phenylalanine biosynthetic intermediate phenylpyruvate can serve as an amino acceptor in tryptophan-dependent auxin biosynthesis, thus facilitating crosstalk between these two distinct primary metabolic pathways.

    • Joseph H. Lynch
    • , Yichun Qian
    • , Longyun Guo
    • , Itay Maoz
    • , Xing-Qi Huang
    • , Alekzander S. Garcia
    • , Gordon Louie
    • , Marianne E. Bowman
    • , Joseph P. Noel
    • , John A. Morgan
    •  & Natalia Dudareva
  • Article |

    The side chain interaction within the short disordered segment of yeast prion protein Sup35 could affect the conformation of the main chain, alter the transmission barrier between species and regulate its cross-seeding activity.

    • Toshinobu Shida
    • , Yuji O. Kamatari
    • , Takao Yoda
    • , Yoshiki Yamaguchi
    • , Michael Feig
    • , Yumiko Ohhashi
    • , Yuji Sugita
    • , Kazuo Kuwata
    •  & Motomasa Tanaka
  • Article |

    Drug combinations consisting of two cell death-targeting drugs are enriched for antagonism and ‘single-agent dominance’, where the faster-acting drug suppresses the slower-acting drug due to inhibitory crosstalk between cell death pathways.

    • Ryan Richards
    • , Hannah R. Schwartz
    • , Megan E. Honeywell
    • , Mariah S. Stewart
    • , Peter Cruz-Gordillo
    • , Anna J. Joyce
    • , Benjamin D. Landry
    •  & Michael J. Lee
  • Article |

    A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal adenocarcinoma.

    • Fleur M. Ferguson
    • , Behnam Nabet
    • , Srivatsan Raghavan
    • , Yan Liu
    • , Alan L. Leggett
    • , Miljan Kuljanin
    • , Radha L. Kalekar
    • , Annan Yang
    • , Shuning He
    • , Jinhua Wang
    • , Raymond W. S. Ng
    • , Rita Sulahian
    • , Lianbo Li
    • , Emily J. Poulin
    • , Ling Huang
    • , Jost Koren
    • , Nora Dieguez-Martinez
    • , Sergio Espinosa
    • , Zhiyang Zeng
    • , Cesear R. Corona
    • , James D. Vasta
    • , Ryoma Ohi
    • , Taebo Sim
    • , Nam Doo Kim
    • , Wayne Harshbarger
    • , Jose M. Lizcano
    • , Matthew B. Robers
    • , Senthil Muthaswamy
    • , Charles Y. Lin
    • , A. Thomas Look
    • , Kevin M. Haigis
    • , Joseph D. Mancias
    • , Brian M. Wolpin
    • , Andrew J. Aguirre
    • , William C. Hahn
    • , Kenneth D. Westover
    •  & Nathanael S. Gray
  • Article |

    Synthetic circuit-host interactions affect the performance synthetic biology systems. Analysis of two bi-stable switch circuits reveals differential effects of host growth on circuit memory, which is dependent on the network topology of the circuit.

    • Rong Zhang
    • , Jiao Li
    • , Juan Melendez-Alvarez
    • , Xingwen Chen
    • , Patrick Sochor
    • , Hanah Goetz
    • , Qi Zhang
    • , Tian Ding
    • , Xiao Wang
    •  & Xiao-Jun Tian
  • Article |

    Systematic characterization of codons using the unnatural base pair dNaM·dTPT3 leads to the discovery of nine new functional codon–anticodon pairs, three of which are shown to be orthogonally decoded by ribosomes and allow incorporation of up to three noncanonical amino acids in Escherichia coli.

    • Emil C. Fischer
    • , Koji Hashimoto
    • , Yorke Zhang
    • , Aaron W. Feldman
    • , Vivian T. Dien
    • , Rebekah J. Karadeema
    • , Ramkrishna Adhikary
    • , Michael P. Ledbetter
    • , Ramanarayanan Krishnamurthy
    •  & Floyd E. Romesberg