Chemical biology

  • Article
    | Open Access

    Mutation of the C-terminal extension of 5′-aminolevulinate synthase 2 (ALAS2) is the molecular cause for X-linked protoporphyria, but the underlying mechanism is unclear. Based on crystal structures and MD simulations of ALAS2, the authors here show how the C-terminal extension regulates ALAS2 activity.

    • Henry J. Bailey
    • , Gustavo A. Bezerra
    • , Jason R. Marcero
    • , Siladitya Padhi
    • , William R. Foster
    • , Elzbieta Rembeza
    • , Arijit Roy
    • , David F. Bishop
    • , Robert J. Desnick
    • , Gopalakrishnan Bulusu
    • , Harry A. Dailey Jr
    •  & Wyatt W. Yue
  • Article
    | Open Access

    Sequestration of reactants in lipid vesicles is a strategy prevalent in biological systems to raise the rate and specificity of chemical reactions. Here, the authors show that micelle-assisted reactions facilitate native chemical ligation between a peptide-thioester and a Cys-peptide modified by a lipid-like moiety.

    • Shuaijiang Jin
    • , Roberto J. Brea
    • , Andrew K. Rudd
    • , Stuart P. Moon
    • , Matthew R. Pratt
    •  & Neal K. Devaraj
  • Article
    | Open Access

    Cyclin-dependent kinase (CDK) inhibitors are widely used both in the clinic and for basic research aimed at dissecting the specific cellular functions of specific CDKs. Here, the authors report the development of a panel of fluorescent reporter probes and provide a comprehensive profile of the inhibitory activity of several CDK inhibitors towards all 21 CDKs in living cells.

    • Carrow I. Wells
    • , James D. Vasta
    • , Cesear R. Corona
    • , Jennifer Wilkinson
    • , Chad A. Zimprich
    • , Morgan R. Ingold
    • , Julie E. Pickett
    • , David H. Drewry
    • , Kathryn M. Pugh
    • , Marie K. Schwinn
    • , Byounghoon (Brian) Hwang
    • , Hicham Zegzouti
    • , Kilian V. M. Huber
    • , Mei Cong
    • , Poncho L. Meisenheimer
    • , Timothy M. Willson
    •  & Matthew B. Robers
  • Article
    | Open Access

    Control of cysteine reactivity is of paramount importance for the synthesis of proteins using native chemical ligation. Here, the authors report a readily cleavable N-selenoethyl group attached to cysteine and apply it to the modular assembly of linear and cyclic polypeptides.

    • Vincent Diemer
    • , Nathalie Ollivier
    • , Bérénice Leclercq
    • , Hervé Drobecq
    • , Jérôme Vicogne
    • , Vangelis Agouridas
    •  & Oleg Melnyk
  • Article
    | Open Access

    The gut microbiota can alter the effects of anticancer fluoropyrimidines such as 5-fluorodeoxyuridine (FUdR) in the model organism C. elegans. Here, the authors show that these effects are further affected by diet, and dietary thymidine and serine increase FUdR toxicity in C. elegans via different mechanisms.

    • Wenfan Ke
    • , James A. Saba
    • , Cong-Hui Yao
    • , Michael A. Hilzendeger
    • , Anna Drangowska-Way
    • , Chintan Joshi
    • , Vinod K. Mony
    • , Shawna B. Benjamin
    • , Sisi Zhang
    • , Jason Locasale
    • , Gary J. Patti
    • , Nathan Lewis
    •  & Eyleen J. O’Rourke
  • Article
    | Open Access

    The low curation of existing nanomaterials’s databases is limiting their application in modeling studies. Here the authors report a publicly available nanomaterial database that contains annotated nanostructures of diverse nanomaterials immediately available for modeling research studies.

    • Xiliang Yan
    • , Alexander Sedykh
    • , Wenyi Wang
    • , Bing Yan
    •  & Hao Zhu
  • Article
    | Open Access

    Protein-protein interactions are fundamental to the regulation of protein activity and cellular phyisology. Here the authors present Split Intein-Mediated Protein Ligation, which uses bait and prey proteins fused to intein fragments to generate single intact proteins upon interaction.

    • Zhong Yao
    • , Farzaneh Aboualizadeh
    • , Jason Kroll
    • , Indira Akula
    • , Jamie Snider
    • , Anna Lyakisheva
    • , Priscilla Tang
    • , Max Kotlyar
    • , Igor Jurisica
    • , Mike Boxem
    •  & Igor Stagljar
  • 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
    • , Taehwan Yang
    • , Penghao Xu
    • , Gary Newnam
    • , Havva Keskin
    • , Waleed M. M. El-Sayed
    • , Anton V. Bryksin
    • , Sijia Tao
    • , Nicole E. Bowen
    • , Raymond F. Schinazi
    • , Baek Kim
    • , Kyung Duk Koh
    • , Fredrik O. Vannberg
    •  & 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
    • , Shawna Organ
    • , Nozomu Sakai
    • , Fengling Li
    • , Levon Halabelian
    • , Suzanne Ackloo
    • , Amber L. Couzens
    • , Mohammad Eram
    • , David Dilworth
    • , Hideto Fukushi
    • , Rachel Harding
    • , Carlo C. dela Seña
    • , Tsukasa Sugo
    • , Kozo Hayashi
    • , David McLeod
    • , Carlos Zepeda
    • , Ahmed Aman
    • , Maria Sánchez-Osuna
    • , Eric Bonneil
    • , Shinji Takagi
    • , Rima Al-Awar
    • , Mike Tyers
    • , Stephane Richard
    • , Masayuki Takizawa
    • , Anne-Claude Gingras
    • , Cheryl H. Arrowsmith
    • , Masoud Vedadi
    • , Peter J. Brown
    • , Hiroshi Nara
    •  & 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
    • , Yuki Goto
    • , Taro Ozaki
    • , Shumpei Asamizu
    • , Yoshinori Sugai
    • , Hiroaki Suga
    •  & Hiroyasu Onaka
  • Article
    | Open Access

    Chemical modification of proteins can be used to decipher function or use that function for therapeutic purposes. Here, the authors insert synthetic peptides via tandem protein trans-splicing to add post-translational modifications or non-canonical amino acids.

    • K. K. Khoo
    • , I. Galleano
    • , F. Gasparri
    • , R. Wieneke
    • , H. Harms
    • , M. H. Poulsen
    • , H. C. Chua
    • , M. Wulf
    • , R. Tampé
    •  & S. A. Pless
  • 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
    • , Andrew W. Woodham
    • , Eileen Daley
    • , Naomi Suminski
    • , Thomas J. Gardella
    •  & 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
    • , Agnès Zettor
    • , Amir Pandi
    • , Angelo Cardoso Batista
    • , Paul Soudier
    •  & 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
    • , Akiho Kaneko
    • , Kazuma Murakami
    • , Kazuhiro Irie
    • , Masatoshi Murai
    • , Hideto Miyoshi
    • , Shingo Dan
    • , Kumi Kawaji
    • , Hironori Hayashi
    • , Eiichi N. Kodama
    • , Aki Hori
    • , Emil Salim
    • , Takayuki Kuraishi
    • , Naoya Hirata
    • , Yasunari Kanda
    •  & 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
    • , Rui Hu
    • , Wesley L. Cai
    • , Yao Li
    • , Shiyao Pei
    • , Hongyin Sun
    • , Cong Peng
    • , Jiali Li
    • , Rui Ye
    • , Qiaohong Yang
    • , Nenghui Wang
    • , Yongguang Tao
    • , Xiang Chen
    •  & 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
    • , David Rooklin
    • , Arthur Hauenstein
    • , Seong Ho Hong
    • , Archana Gautam
    • , Hao Wu
    • , Yingkai Zhang
    • , Ethel Cesarman
    •  & 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
    • , Woojoo E. Kim
    • , Tony D. Davis
    • , Aochiu Chen
    • , Thomas G. Bartholow
    • , James J. La Clair
    • , J. Andrew McCammon
    • , Joseph P. Noel
    •  & 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
    • , Simone Pellegrino
    • , Aydar Bikmullin
    • , Wen-ti Liu
    • , Azat Gabdulkhakov
    • , Amr Al Shebel
    • , Alexander Golubev
    • , Denis Zeyer
    • , Natalie Trachtmann
    • , Georg A. Sprenger
    • , Shamil Validov
    • , Konstantin Usachev
    • , Gulnara Yusupova
    •  & 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
    • , Conor Lawless
    • , Marcos Cámara-Donoso
    • , Onur Sen
    • , Kosuke Sako
    • , Toru Hirota
    • , Hiroshi Kimura
    •  & 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
    • , Shunyu Yao
    • , Xinjie Shi
    • , Longxian Lv
    •  & Yi-Ling Du
  • Article
    | Open Access

    Near-infrared fluorescent probes hold great potential for biomedical imaging but most bind to albumin, generating unspecific fluorescence. Here the authors identify the acceptor (A) group as responsible and design a new A group that avoids capture by albumin, and apply it to imaging liver fibrosis in vivo.

    • Panfei Xing
    • , Yiming Niu
    • , Ruoyu Mu
    • , Zhenzhen Wang
    • , Daping Xie
    • , Huanling Li
    • , Lei Dong
    •  & Chunming Wang
  • 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
    • , Raoul N. Frese
    •  & 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
    • , Michelle Coleman
    • , Phoenicia Quach
    • , Christopher Whidbey
    • , Jose Justicia
    • , Ruben Tapia
    • , Raquel Casares
    • , Alba Millán
    • , Ali Haidour
    • , Javier Rodriguez Granger
    • , Jay Vornhagen
    • , Verónica Santana-Ufret
    • , Sean Merillat
    • , Kristina Adams Waldorf
    • , Juan Manuel Cuerva
    •  & 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
    • , Xin Zhang
    • , Qianjin Kang
    • , Dan Zhang
    • , Lili Zhang
    • , Linquan Bai
    •  & 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
    • , Maria Lígia Sousa
    •  & 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
    • , Catrina A. Reed
    • , Andreas Ehnbom
    • , Peng-Hsun Chase Chen
    • , Jared S. Morse
    • , Yadagirri Kurra
    • , Lisa M. Pérez
    • , Shiqing Xu
    •  & 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
    • , Tine Tricot
    • , Ilaria Elia
    • , Laura Ordovas
    • , Frank Jacobs
    • , Jennifer One
    • , Jonathan De Smedt
    • , Guy Eelen
    • , Matthew Bird
    • , Philip Roelandt
    • , Ginevra Doglioni
    • , Kim Vriens
    • , Matteo Rossi
    • , Marta Aguirre Vazquez
    • , Thomas Vanwelden
    • , François Chesnais
    • , Adil El Taghdouini
    • , Mustapha Najimi
    • , Etienne Sokal
    • , David Cassiman
    • , Jan Snoeys
    • , Mario Monshouwer
    • , Wei-Shou Hu
    • , Christian Lange
    • , Peter Carmeliet
    • , Sarah-Maria Fendt
    •  & 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
    • , Yu Zhang
    • , Zhimin Wang
    • , Dailiang Zhang
    • , Lei He
    • , Liping Qiu
    • , Jianhui Jiang
    •  & 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
    • , Adrian Scaffidi
    • , Kim T. Melville
    • , Sabrina F. Davies
    • , Charles S. Bond
    • , Steven M. Smith
    • , Gavin R. Flematti
    •  & 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
    • , Idan Steinberg
    • , Tom Haywood
    •  & 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
    • , Brian E. Krumm
    • , Kuglae Kim
    • , Els Pardon
    • , Reid H. J. Olsen
    • , Sheng Wang
    • , Shicheng Zhang
    • , Jeffrey F. Diberto
    • , Noah Sciaky
    • , F. Ivy Carroll
    • , Jan Steyaert
    • , Daniel Wacker
    •  & 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
    • , Elena A. Andreeva
    • , Aaron S. Brewster
    • , Mark S. Hunter
    • , Raymond G. Sierra
    • , Jean-Marie Teulon
    • , Iris D. Young
    • , Niamh Burke
    • , Tilman A. Grünewald
    • , Joël Beaudouin
    • , Irina Snigireva
    • , Maria Teresa Fernandez-Luna
    • , Alister Burt
    • , Hyun-Woo Park
    • , Luca Signor
    • , Jayesh A. Bafna
    • , Rabia Sadir
    • , Daphna Fenel
    • , Elisabetta Boeri-Erba
    • , Maria Bacia
    • , Ninon Zala
    • , Frédéric Laporte
    • , Laurence Després
    • , Martin Weik
    • , Sébastien Boutet
    • , Martin Rosenthal
    • , Nicolas Coquelle
    • , Manfred Burghammer
    • , Duilio Cascio
    • , Michael R. Sawaya
    • , Mathias Winterhalter
    • , Enrico Gratton
    • , Irina Gutsche
    • , Brian Federici
    • , Jean-Luc Pellequer
    • , Nicholas K. Sauter
    •  & 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
    • , Jens C. Frisvad
    • , Jane L. Nybo
    • , Sebastian Theobald
    • , Sara Kildgaard
    • , Thomas Isbrandt Petersen
    • , Alan Kuo
    • , Atsushi Sato
    • , Ellen K. Lyhne
    • , Martin E. Kogle
    • , Ad Wiebenga
    • , Roland S. Kun
    • , Ronnie J. M. Lubbers
    • , Miia R. Mäkelä
    • , Kerrie Barry
    • , Mansi Chovatia
    • , Alicia Clum
    • , Chris Daum
    • , Sajeet Haridas
    • , Guifen He
    • , Kurt LaButti
    • , Anna Lipzen
    • , Stephen Mondo
    • , Jasmyn Pangilinan
    • , Robert Riley
    • , Asaf Salamov
    • , Blake A. Simmons
    • , Jon K. Magnuson
    • , Bernard Henrissat
    • , Uffe H. Mortensen
    • , Thomas O. Larsen
    • , Ronald P. de Vries
    • , Igor V. Grigoriev
    • , Masayuki Machida
    • , Scott E. Baker
    •  & 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
    • , Junichi Enoki
    • , Roland Meier
    • , Bernhard Schönenberger
    • , Roland Wohlgemuth
    • , Robert Kourist
    • , Felix Niemeyer
    • , David van Niekerk
    • , Christopher Bräsen
    • , Jochen Niemeyer
    • , Jacky Snoep
    •  & Bettina Siebers
  • Article
    | Open Access

    The D2 dopamine receptor (DRD2) is one of the most well-established therapeutic targets for neuropsychiatric and endocrine disorders. Here, the authors report the crystal structure of the antipsychotic drug haloperidol bound to DRD2 via an extended binding pocket that distinguishes it from other D2-like subtypes.

    • Luyu Fan
    • , Liang Tan
    • , Zhangcheng Chen
    • , Jianzhong Qi
    • , Fen Nie
    • , Zhipu Luo
    • , Jianjun Cheng
    •  & Sheng Wang
  • 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
    • , Paul E. Reyes-Gutierrez
    • , Martin Culka
    • , Hana Šanderová
    • , Martin Hubálek
    • , Lubomír Rulíšek
    • , Josef Cvačka
    • , Libor Krásný
    •  & 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
    • , Annette E. Langkilde
    • , Peter Westh
    • , Anne S. Meyer
    • , Jane W. Agger
    •  & 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
    • , Guoce An
    • , Mengdi Shang
    • , Zenghui Cui
    • , Gong Chen
    • , Zhen Xi
    •  & 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
    • , Åsmund K. Røhr
    •  & 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
    • , X. Edward Zhou
    • , Ravi Kumar Verma
    • , Parker W. de Waal
    • , Wonjo Jang
    • , Ting-Hai Xu
    • , Lei Wang
    • , Xing Meng
    • , Gongpu Zhao
    • , Yanyong Kang
    • , Karsten Melcher
    • , Hao Fan
    • , Nevin A. Lambert
    • , H. Eric Xu
    •  & 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
    • , Banumathi Sankaran
    •  & 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
    • , Joseph J. Muldoon
    • , Hailey I. Edelstein
    • , Neda Bagheri
    •  & 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
    • , Josef M. Penninger
    •  & 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
    • , Polina V. Verkhusha
    • , Sara K. Donnelly
    • , Maren Hülsemann
    • , Jori Virtanen
    • , Henna M. Moore
    • , Maria K. Vartiainen
    • , Louis Hodgson
    •  & 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
    • , Hyojin Kim
    •  & Martin Fussenegger
  • 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
    • , Adam Shellard
    • , Chiara Zambarda
    • , Joachim Pius Spatz
    • , Philippe Marcq
    • , Roberto Mayor
    • , Richard Wombacher
    •  & Elisabetta Ada Cavalcanti-Adam