Featured
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Article
| Open AccessA molecular switch orchestrates enzyme specificity and secretory granule morphology
Regulated secretion is an essential process that requires packing and maturation of cargo proteins in membranous secretory granules. Here, authors identify a gene, pgant9, that influences the glycosylation status of the secretory cargo as well as the structure of secretory granules within the Drosophila salivary gland.
- Suena Ji
- , Nadine L. Samara
- & Kelly G. Ten Hagen
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Article
| Open AccessDe novo targeting to the cytoplasmic and luminal side of bacterial microcompartments
Bacterial microcompartments (BMCs) are protein-bound organelles encapsulating segments of metabolic pathways. Here the authors utilize specific de novo coiled-coil protein-protein interactions to display proteins on the outer or inner surface of BMCs.
- Matthew J. Lee
- , Judith Mantell
- & Martin J. Warren
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Article
| Open AccessIntertidal exposure favors the soft-studded armor of adaptive mussel coatings
There is interest in the development of mussel inspired materials; however, this requires an understanding of the materials. Here, the authors report on an investigation into the properties of mussel cuticle from different species that challenges conventional wisdom about particle filled composites.
- Christophe A. Monnier
- , Daniel G. DeMartini
- & J. Herbert Waite
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Article
| Open AccessDirect quality control of glycoengineered erythropoietin variants
Several therapeutics are glycosylated proteins, yet the analysis of their specific glycosylation patterns remains challenging. Here the authors demonstrate an approach for the detailed characterization of glycosylated biopharmaceuticals applied to the determination of the glycoproteoform profile of glycoengineered variants of erythropoietin.
- Tomislav Čaval
- , Weihua Tian
- & Albert J. R. Heck
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Article
| Open AccessSingle-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells
Plasmacytoid dendritic cells (pDC) are a pivotal component of the immune system. Here, the authors utilize single-cell microfluidics to interrogate the human pDC compartment and reveal a subset of type I IFN secreting pDCs that is regulated by stochastic gene expression and amplified by microenvironmental cues.
- Florian Wimmers
- , Nikita Subedi
- & Jurjen Tel
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Article
| Open AccessExtension of the crRNA enhances Cpf1 gene editing in vitro and in vivo
Optimization of the recently discovered Class 2 CRISPR protein Cpf1 has the potential to promote its applications in gene editing and therapeutics. Here, the authors find that extending the 5′ end of the crRNA can increase both the editing efficiency and delivery of Cpf1 in vitro and in vivo.
- Hyo Min Park
- , Hui Liu
- & Kunwoo Lee
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Article
| Open AccessThe VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner
Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells
- Mette Ø. Agerbæk
- , Sara R. Bang-Christensen
- & Ali Salanti
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Article
| Open AccessVisual and modular detection of pathogen nucleic acids with enzyme–DNA molecular complexes
Rapid, visual detection of pathogens is important for point-of-care diagnostics. Here the authors present enVision, which uses enzyme-DNA complexes to detect pathogen nucleic acids and provide a rapid, smartphone compatible readout.
- Nicholas R. Y. Ho
- , Geok Soon Lim
- & Huilin Shao
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Article
| Open AccessA biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy
The promise of stem cell therapy for treating central nervous system disease is limited by low stem cell transplantation survival rates and poorly controlled cell fate. Here, the authors develop a biodegradable nanoscaffold for spinal cord injury that enhances transplantation and differentiation of neural stem cells and delivers drugs.
- Letao Yang
- , Sy-Tsong Dean Chueng
- & Ki-Bum Lee
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Article
| Open AccessMonitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
Current sensors for intracellular H2O2 are not sensitive enough to detect all biologically relevant H2O2 fluctuations. Here the authors develop a peroxiredoxin-2-based FRET probe that is sensitive enough to measure changes in H2O2 concentration in response to the cancer therapeutic piperlongumine.
- Troy F. Langford
- , Beijing K. Huang
- & Hadley D. Sikes
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Article
| Open AccessDeep learning to predict the lab-of-origin of engineered DNA
The synthetic biology era has seen a rapidly growing number of engineered DNA sequences. Here, the authors develop a deep learning method to predict the lab-of-origin of a DNA sequence based on hidden design signatures.
- Alec A. K. Nielsen
- & Christopher A. Voigt
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Article
| Open AccessNon plasmonic semiconductor quantum SERS probe as a pathway for in vitro cancer detection
Surface enhanced Raman scattering is a bio-analytical tool and the development and optimisation of probes is an active area of investigation. Here, the authors report on the development and testing of biocompatible semiconductor zinc oxide quantum probes on a platform for cell adhesion and analysis.
- Rupa Haldavnekar
- , Krishnan Venkatakrishnan
- & Bo Tan
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Article
| Open AccessGlobal rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative
Reducing aerobic ethanol production, a phenomenon referred to as the Crabtree effect, may open up new perspectives for using yeast as a cell factory. Here, the authors turn the Crabtree-positive yeast into Crabtree negative by combined engineering of cytosolic acetyl-CoA metabolism and mutating the RNA polymerase II mediator complex.
- Zongjie Dai
- , Mingtao Huang
- & Jens Nielsen
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Article
| Open AccessSensor-regulator and RNAi based bifunctional dynamic control network for engineered microbial synthesis
Engineering dynamic control can improve microbial production of target chemicals. Here, the authors design a sensor-regulator and RNAi based bifunctional dynamic control network that can simultaneously and independently turn up and down cellular metabolism for engineered muconic acid production in E. coli.
- Yaping Yang
- , Yuheng Lin
- & Yajun Yan
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Article
| Open AccessInterleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
Human pluripotent stem cell-derived intestinal organoids (hIOs) are a useful model with which to study intestinal development and disease, but they require in vivo maturation to resemble adult tissue. Here, the authors show that T lymphocyte-derived IL-2 induces hIO maturation in vitro through the activation of STAT3.
- Kwang Bo Jung
- , Hana Lee
- & Mi-Young Son
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Article
| Open AccessTopical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity
Ferumoxytol is a nanoparticle formulation approved for systemic use to treat iron deficiency. Liu et al. show that topical use of ferumoxytol, in combination with low concentrations of H2O2, disrupts intractable oral biofilms and prevents tooth decay in vitro and in an animal model.
- Yuan Liu
- , Pratap C. Naha
- & Hyun Koo
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Article
| Open AccessControllable protein phase separation and modular recruitment to form responsive membraneless organelles
Designer organelles with new biochemical functionalities are of great interest in synthetic biology and cellular engineering. Here the authors present a single-protein-based platform for generating synthetic membraneless compartments that is capable of enzymatically-triggered alterations to phase behavior and of recruiting and concentrating cargo proteins.
- Benjamin S. Schuster
- , Ellen H. Reed
- & Daniel A. Hammer
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Perspective
| Open AccessDesigning with living systems in the synthetic yeast project
Synthetic biology often views the organism as a chassis into which a circuit can be inserted. Here the authors explore the idea of the organism as a core aspect of design, aiding researchers in navigating the genetic space opened up by SCRaMbLE.
- Erika Szymanski
- & Jane Calvert
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Article
| Open AccessPairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells
A rigorous understanding of off-target effects is necessary for SaCas9 to be used in therapeutic genome editing. Here the authors measure SaCas9 mismatch tolerance across a pairwise library screen of 88,000 guides and targets in human cells and develop a model which ranks off-target sites.
- Josh Tycko
- , Luis A. Barrera
- & Patrick D. Hsu
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Article
| Open AccessSensitive and powerful single-cell RNA sequencing using mcSCRB-seq
Single-cell RNA-barcoding and sequencing is an efficient, genome-wide method to characterize cellular identities. Here the authors systematically evaluate the protocol and develop molecular crowding SCRB-seq with improved sensitivity and cost-efficiency.
- Johannes W. Bagnoli
- , Christoph Ziegenhain
- & Wolfgang Enard
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Article
| Open AccessNIR-II nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer
Real-time fluorescence imaging in the NIR-II region offers non-invasive detection of ovarian metastatic tumors and their image-guided surgery. Here the authors describe NIR-II nanoprobes in vivo assembly for detection of disseminated ovarian cancer.
- Peiyuan Wang
- , Yong Fan
- & Fan Zhang
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Article
| Open AccessProgrammed loading and rapid purification of engineered bacterial microcompartment shells
Bacterial microcompartments are protein-bound organelles encapsulating segments of metabolic pathways. Here the authors functionalise shell proteins to facilitate facile purification and enable cargo encapsulation via covalent linkage.
- Andrew Hagen
- , Markus Sutter
- & Cheryl A. Kerfeld
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Article
| Open AccessMetaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease
Gut microbial dysbiosis has been implicated in the pathogenesis of inflammatory bowel disease. Here, the authors examine host-microbiota protein interactions that occur in inflammatory bowel disease; they show an upregulation in proteins related to antimicrobial activities, and alterations in intestinal extracellular vesicles that are associated with aberrant microbiota-interactions.
- Xu Zhang
- , Shelley A. Deeke
- & Daniel Figeys
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Article
| Open AccessSimplified ChIP-exo assays
While ChIP-exo is low noise and highly informative regarding genome-wide binding proteins, libraries are difficult to construct. Here the authors present a simplified ChIP-exo method for high-resolution detection of interactions.
- Matthew J. Rossi
- , William K. M. Lai
- & B. Franklin Pugh
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Article
| Open AccessMapping the sensing spots of aerolysin for single oligonucleotides analysis
Nanopores are an emerging powerful single-molecule method of DNA sequencing. Here the authors map the structure of aerolysin for use as a nanopore and show detection of modified and unmodified nucleobases.
- Chan Cao
- , Meng-Yin Li
- & Yi-Tao Long
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Article
| Open AccessInjectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing
To improve trauma survival and surgical outcomes, hemostatic agents are needed. Here, the authors report on the development of injectable, biocompatible carbon nanotube reinforced quaternized chitosan cryogels with shape memory, conductivity and antibacterial properties for hemostatic control.
- Xin Zhao
- , Baolin Guo
- & Peter X. Ma
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Article
| Open AccessControlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation
X-ray radiation has excellent tissue penetration depth, making it a useful trigger for deep tissue cancer therapy. Here, the authors design X-ray triggered drug/gene-loaded liposomes by embedding photosensitizers and gold nanoparticles in the liposome bilayer, and demonstrate their efficacy in cancer and gene therapy.
- Wei Deng
- , Wenjie Chen
- & Ewa M. Goldys
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Article
| Open AccessSingle-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery
The ability to produce homogeneous glycoproteins is expected to advance fundamental understanding in glycoscience, but current in vivo-based production systems have several limitations. Here, the authors develop an E. coli extract-based one-pot system for customized production of N-linked glycoproteins.
- Thapakorn Jaroentomeechai
- , Jessica C. Stark
- & Matthew P. DeLisa
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Article
| Open AccessTools for engineering coordinated system behaviour in synthetic microbial consortia
The engineering of synthetic microbial communities necessitates the use of synthetic, orthogonal cell-to-cell communication channels. Here the authors present a library of characterised AHL-receiver devices and a software tool for the automatic identification of non-interfering chemical communication channels.
- Nicolas Kylilis
- , Zoltan A. Tuza
- & Karen M. Polizzi
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Article
| Open AccessRed blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude
Unwanted uptake in the liver and limited accumulation in target organs is a major obstacle to targeted drug delivery. Here, the authors report on the hitchhiking of nanocarriers on red blood cells and the targeted upstream delivery to different target organs in mice, pigs and ex vivo human lungs.
- Jacob S. Brenner
- , Daniel C. Pan
- & Vladimir Muzykantov
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Article
| Open AccessAAV vector-mediated in vivo reprogramming into pluripotency
In vivo reprogramming of somatic cells is hampered by the need for vectors to express the OKSM factors in selected organs. Here the authors report new AAV-based vectors capable of in vivo reprogramming at low doses.
- Elena Senís
- , Lluc Mosteiro
- & Dirk Grimm
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Article
| Open AccessEngineering circular RNA for potent and stable translation in eukaryotic cells
Circular RNAs have recently been shown to have protein-coding potential. Here the authors design a self-splicing RNA that, when circularized, provides for stable high-yield protein production.
- R. Alexander Wesselhoeft
- , Piotr S. Kowalski
- & Daniel G. Anderson
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Article
| Open AccessHeavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
Resistance of gRNA to ubiquitous ribonucleases is required for CRISPR-Cas9-based therapeutics. Here, the authors explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor, and identify modified versions that are more potent and stable than their unmodified counterparts in editing human cells.
- Aamir Mir
- , Julia F. Alterman
- & Erik J. Sontheimer
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Article
| Open AccessHuman pluripotent reprogramming with CRISPR activators
CRISPRa is an attractive tool for cellular reprogramming due to its multiplexing capacity and direct targeting of genomic loci. Here the authors demonstrate the reprogramming of human fibroblasts into iPSCs, which is enhanced by targeting a conserved Alu-motif.
- Jere Weltner
- , Diego Balboa
- & Timo Otonkoski
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Article
| Open AccessRapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers
Penetration of the mucus and tumor interstitial matrix is an important consideration for drug delivery devices. Here, the authors report on a study into the optimization of rigidity for the transport of nanoparticles through biological hydrogels using core-shell polymer-lipid nanoparticles.
- Miaorong Yu
- , Lu Xu
- & Huajian Gao
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Article
| Open AccessPeptide density targets and impedes triple negative breast cancer metastasis
The C-X-C chemokine receptor type 4 (CXCR4) pathway is a key regulator of cancer metastasis. Here, the authors present a method to block CXCR4 and thereby inhibit breast cancer metastasis by developing a liposome that presents CXCR4-binding peptides in a multivalent fashion.
- Daxing Liu
- , Peng Guo
- & Debra Auguste
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Article
| Open AccessSynthetic molecular evolution of hybrid cell penetrating peptides
Therapeutic peptide nucleic acids can be delivered into cells by conjugation to cell penetrating peptides (CPPs), but efficiency is usually low. Here the authors use synthetic molecular evolution and a luciferase-based library screen to generate new CPPs with improved efficiency and lower toxicity.
- W. Berkeley Kauffman
- , Shantanu Guha
- & William C. Wimley
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Article
| Open Access2D transition metal dichalcogenides with glucan multivalency for antibody-free pathogen recognition
The detection of pathogenic microorganisms is key consideration for safety across a wide range of fields. Here, the authors report on the simultaneous exfoliation and functionalisation of transition metal dichalcogenides with dextran for antibody-free detection of pathogenic Escherichia coli.
- Tae Woog Kang
- , Juhee Han
- & Jong-Ho Kim
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Article
| Open AccessSynthetic CRISPR-Cas gene activators for transcriptional reprogramming in bacteria
The absence of effective gene activators in bacteria limits regulated expression programs. Here the authors design synthetic bacterial CRISPR-Cas transcriptional activators that can be used to construct multi-gene programs of activation and repression.
- Chen Dong
- , Jason Fontana
- & Jesse G. Zalatan
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Article
| Open AccessIn utero nanoparticle delivery for site-specific genome editing
The correction of genetic defects in utero could allow for improved outcomes of gene therapy. Here, the authors demonstrate safe delivery of nanoparticles to fetal mouse tissues, and show that nanoparticles containing peptide nucleic acids to edit the beta-globin gene are effective in a mouse model of beta-thalassemia.
- Adele S. Ricciardi
- , Raman Bahal
- & W. Mark Saltzman
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Article
| Open AccessmiR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models
Depletion of the splicing factors MBNL 1 and 2 causes myotonic dystrophy. Here, the authors show that miR-23b and miR-218 target MBNL proteins, and that antagonists to these miRNAs rescue mis-splicing events in myoblasts and boost MBNL expression and rescue pathology in mouse models.
- Estefania Cerro-Herreros
- , Maria Sabater-Arcis
- & Ruben Artero
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Article
| Open AccessPooled CRISPR interference screening enables genome-scale functional genomics study in bacteria with superior performance
Systemic investigation of the bacterial genome is essential for both basic microbiology and bioengineering. Here the authors demonstrate CRISPRi pooled screening as a high-throughput tool for identifying gene and phenotype associations in bacteria.
- Tianmin Wang
- , Changge Guan
- & Xin-Hui Xing
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Article
| Open AccessSpontaneous buckling of contractile poroelastic actomyosin sheets
Active matter composed of filaments and molecular motors can contract. Here, the authors report the spontaneous out-of-plane buckling of reconstituted contracting poroelastic actomyosin sheets in the absence of external cues.
- Y. Ideses
- , V. Erukhimovitch
- & A. Bernheim-Groswasser
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Article
| Open AccessA microfluidics platform for combinatorial drug screening on cancer biopsies
Cancer patients exhibit specific sensitivities toward drug combinations that cannot be easily predicted. Here the authors setup a microfluidic platform that allows testing of multiple drug combinations correctly predicting sensitivity in vivo and they use it on patients biopsies to define effective drugs.
- Federica Eduati
- , Ramesh Utharala
- & Christoph A. Merten
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Article
| Open AccessA synthetic enzyme built from DNA flips 107 lipids per second in biological membranes
Mimicking enzyme function and improving upon it is a challenge facing nanotechnology. Here the authors design a DNA nanostructure that catalyzes the transport of lipids between bilayers at a rate three orders of magnitude higher than biological enzymes.
- Alexander Ohmann
- , Chen-Yu Li
- & Aleksei Aksimentiev
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Article
| Open AccessUrinary cell-free DNA is a versatile analyte for monitoring infections of the urinary tract
Urinary tract infections are one of the most common infections in humans. Here, the authors use urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in bacterial and viral urinary tract infections, and show that it is a versatile analyte for monitoring urinary tract infections.
- Philip Burnham
- , Darshana Dadhania
- & Iwijn De Vlaminck
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Article
| Open AccessSpatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
Heterogeneity within tumors presents a challenge to cancer treatment. Here, the authors investigate transcriptional heterogeneity in prostate cancer, examining expression profiles of different tissue components and highlighting expression gradients in the tumor microenvironment.
- Emelie Berglund
- , Jonas Maaskola
- & Joakim Lundeberg
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Article
| Open AccessHEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology
In silico models of cells can provide insight into the causes and effects of disease states and reduce the need for in vivo studies. Here, the authors present a kinetic model of hepatocyte metabolism including energy, carbohydrate, lipid and nitrogen metabolism and hormonal and allosteric regulation of enzymatic activity.
- Nikolaus Berndt
- , Sascha Bulik
- & Hermann-Georg Holzhütter
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Article
| Open AccessImproving formaldehyde consumption drives methanol assimilation in engineered E. coli
Engineering E. coli for metabolization of methanol to produce fuels and chemicals has not been fully achieved. Here, the authors combine metabolic engineering and chemical inhibition to improve methanol assimilation and distinguish the role of kinetics and thermodynamics under various culture conditions.
- Benjamin M. Woolston
- , Jason R. King
- & Gregory Stephanopoulos
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