EcoSynther: A Customized Platform To Explore the Biosynthetic Potential in E. coli.

Abstract:

:Developing computational tools for a chassis-centered biosynthetic pathway design is very important for a productive heterologous biosynthesis system by considering enormous foreign biosynthetic reactions. For many cases, a pathway to produce a target molecule consists of both native and heterologous reactions when utilizing a microbial organism as the host organism. Due to tens of thousands of biosynthetic reactions existing in nature, it is not trivial to identify which could be served as heterologous ones to produce the target molecule in a specific organism. In the present work, we integrate more than 10,000 E. coli non-native reactions and utilize a probability-based algorithm to search pathways. Moreover, we built a user-friendly Web server named EcoSynther. It is able to explore the precursors and heterologous reactions needed to produce a target molecule in Escherichia coli K12 MG1655 and then applies flux balance analysis to calculate theoretical yields of each candidate pathway. Compared with other chassis-centered biosynthetic pathway design tools, EcoSynther has two unique features: (1) allow for automatic search without knowing a precursor in E. coli and (2) evaluate the candidate pathways under constraints from E. coli physiological states and growth conditions. EcoSynther is available at http://www.rxnfinder.org/ecosynther/ .

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Ding S,Liao X,Tu W,Wu L,Tian Y,Sun Q,Chen J,Hu QN

doi

10.1021/acschembio.7b00605

subject

Has Abstract

pub_date

2017-11-17 00:00:00

pages

2823-2829

issue

11

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章
  • Discovery of Selective RNA-Binding Small Molecules by Affinity-Selection Mass Spectrometry.

    abstract::Recent advances in understanding the relevance of noncoding RNA (ncRNA) to disease have increased interest in drugging ncRNA with small molecules. The recent discovery of ribocil, a structurally distinct synthetic mimic of the natural ligand of the flavin mononucleotide (FMN) riboswitch, has revealed the potential che...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b01013

    authors: Rizvi NF,Howe JA,Nahvi A,Klein DJ,Fischmann TO,Kim HY,McCoy MA,Walker SS,Hruza A,Richards MP,Chamberlin C,Saradjian P,Butko MT,Mercado G,Burchard J,Strickland C,Dandliker PJ,Smith GF,Nickbarg EB

    更新日期:2018-03-16 00:00:00

  • Mechanism-Based Post-Translational Modification and Inactivation in Terpene Synthases.

    abstract::Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesi...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00539

    authors: Kersten RD,Diedrich JK,Yates JR 3rd,Noel JP

    更新日期:2015-11-20 00:00:00

  • Harnessing Fluorine-Sulfur Contacts and Multipolar Interactions for the Design of p53 Mutant Y220C Rescue Drugs.

    abstract::Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-in...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00315

    authors: Bauer MR,Jones RN,Baud MG,Wilcken R,Boeckler FM,Fersht AR,Joerger AC,Spencer J

    更新日期:2016-08-19 00:00:00

  • Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes.

    abstract::Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of g...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00152

    authors: Nasir W,Frank M,Kunze A,Bally M,Parra F,Nyholm PG,Höök F,Larson G

    更新日期:2017-05-19 00:00:00

  • Progressive Stereo Locking (PSL): A Residual Dipolar Coupling Based Force Field Method for Determining the Relative Configuration of Natural Products and Other Small Molecules.

    abstract::Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to all...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00281

    authors: Cornilescu G,Ramos Alvarenga RF,Wyche TP,Bugni TS,Gil RR,Cornilescu CC,Westler WM,Markley JL,Schwieters CD

    更新日期:2017-08-18 00:00:00

  • Identification of a small molecule inhibitor of importin β mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries.

    abstract::In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nu...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb100094k

    authors: Hintersteiner M,Ambrus G,Bednenko J,Schmied M,Knox AJ,Meisner NC,Gstach H,Seifert JM,Singer EL,Gerace L,Auer M

    更新日期:2010-10-15 00:00:00

  • siRNA screen identifies the phosphatase acting on the G protein-coupled thyrotropin-releasing hormone receptor.

    abstract::G protein-coupled receptors (GPCRs) are an ubiquitously expressed class of transmembrane proteins involved in the signal transduction of neurotransmitters, hormones and various other ligands. Their signaling output is desensitized by mechanisms involving phosphorylation, internalization, and dissociation from G protei...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb3004513

    authors: Gehret AU,Hinkle PM

    更新日期:2013-03-15 00:00:00

  • The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase.

    abstract::Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Ther...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00700

    authors: Nguyen A,Nguyen D,Phong Nguyen TX,Sebastiani M,Dörr S,Hernandez-Alba O,Debaene F,Cianférani S,Heine A,Klebe G,Reuter K

    更新日期:2020-11-20 00:00:00

  • Insertions within the Saxitoxin Biosynthetic Gene Cluster Result in Differential Toxin Profiles.

    abstract::The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b00608

    authors: Cullen A,D'Agostino PM,Mazmouz R,Pickford R,Wood S,Neilan BA

    更新日期:2018-11-16 00:00:00

  • Generation of Optogenetically Modified Adenovirus Vector for Spatiotemporally Controllable Gene Therapy.

    abstract::Gene therapy is expected to be utilized for the treatment of various diseases. However, the spatiotemporal resolution of current gene therapy technology is not high enough. In this study, we generated a new technology for spatiotemporally controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b01058

    authors: Takayama K,Mizuguchi H

    更新日期:2018-02-16 00:00:00

  • Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to β-lactams.

    abstract::Rising drug resistance is limiting treatment options for infections by methicillin-resistant Staphylococcus aureus (MRSA). Herein we provide new evidence that wall teichoic acid (WTA) biogenesis is a remarkable antibacterial target with the capacity to destabilize the cooperative action of penicillin-binding proteins ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300413m

    authors: Farha MA,Leung A,Sewell EW,D'Elia MA,Allison SE,Ejim L,Pereira PM,Pinho MG,Wright GD,Brown ED

    更新日期:2013-01-18 00:00:00

  • Chromophore-assisted light inactivation of HaloTag fusion proteins labeled with eosin in living cells.

    abstract::Chromophore-assisted light inactivation (CALI) is a potentially powerful tool for the acute disruption of a target protein inside living cells with high spatiotemporal resolution. This technology, however, has not been widely utilized, mainly because of the lack of an efficient chromophore as the photosensitizing agen...

    journal_title:ACS chemical biology

    pub_type: 信件

    doi:10.1021/cb100431e

    authors: Takemoto K,Matsuda T,McDougall M,Klaubert DH,Hasegawa A,Los GV,Wood KV,Miyawaki A,Nagai T

    更新日期:2011-05-20 00:00:00

  • pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.

    abstract::We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE p...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb500388m

    authors: Karabadzhak AG,An M,Yao L,Langenbacher R,Moshnikova A,Adochite RC,Andreev OA,Reshetnyak YK,Engelman DM

    更新日期:2014-11-21 00:00:00

  • Engineered Reader Proteins for Enhanced Detection of Methylated Lysine on Histones.

    abstract::Histone post-translational modifications (PTMs) are crucial for many cellular processes including mitosis, transcription, and DNA repair. The cellular readout of histone PTMs is dependent on both the chemical modification and histone site, and the array of histone PTMs on chromatin is dynamic throughout the eukaryotic...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00651

    authors: Albanese KI,Krone MW,Petell CJ,Parker MM,Strahl BD,Brustad EM,Waters ML

    更新日期:2020-01-17 00:00:00

  • Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites.

    abstract::BRD4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00058

    authors: Olp MD,Sprague DJ,Goetz CJ,Kathman SG,Wynia-Smith SL,Shishodia S,Summers SB,Xu Z,Statsyuk AV,Smith BC

    更新日期:2020-04-17 00:00:00

  • Cross-Linking Furan-Modified Kisspeptin-10 to the KISS Receptor.

    abstract::Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00396

    authors: Vannecke W,Ampe C,Van Troys M,Beltramo M,Madder A

    更新日期:2017-08-18 00:00:00

  • Quantitative analysis of T cell receptor complex interaction sites using genetically encoded photo-cross-linkers.

    abstract::The T cell receptor (TCR)-cluster of differentiation 3 (CD3) signaling complex plays an important role in initiation of adaptive immune responses, but weak interactions have obstructed delineation of the individual TCR-CD3 subunit interactions during T cell signaling. Here, we demonstrate that unnatural amino acids (U...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb500351s

    authors: Wang W,Li T,Felsovalyi K,Chen C,Cardozo T,Krogsgaard M

    更新日期:2014-09-19 00:00:00

  • Cell-penetrating bisubstrate-based protein kinase C inhibitors.

    abstract::Although protein kinase inhibitors present excellent pharmaceutical opportunities, lack of selectivity and associated therapeutic side effects are common. Bisubstrate-based inhibitors targeting both the high-selectivity peptide substrate binding groove and the high-affinity ATP pocket address this. However, they are t...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300709g

    authors: van Wandelen LT,van Ameijde J,Ismail-Ali AF,van Ufford HC,Vijftigschild LA,Beekman JM,Martin NI,Ruijtenbeek R,Liskamp RM

    更新日期:2013-07-19 00:00:00

  • Stable RAGE-heparan sulfate complexes are essential for signal transduction.

    abstract::RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb4001553

    authors: Xu D,Young JH,Krahn JM,Song D,Corbett KD,Chazin WJ,Pedersen LC,Esko JD

    更新日期:2013-07-19 00:00:00

  • Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae.

    abstract::Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by β-lactam antibiotics. We report herein our structural insights into catalysis by the essentia...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00817

    authors: Bernardo-García N,Mahasenan KV,Batuecas MT,Lee M,Hesek D,Petráčková D,Doubravová L,Branny P,Mobashery S,Hermoso JA

    更新日期:2018-03-16 00:00:00

  • Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily.

    abstract::The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00334

    authors: Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

    更新日期:2017-12-15 00:00:00

  • Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.

    abstract::Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both i...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00222

    authors: Hodge CD,Edwards RA,Markin CJ,McDonald D,Pulvino M,Huen MS,Zhao J,Spyracopoulos L,Hendzel MJ,Glover JN

    更新日期:2015-07-17 00:00:00

  • Profiling Cysteine Reactivity and Oxidation in the Endoplasmic Reticulum.

    abstract::The endoplasmic reticulum (ER) is the initial site of biogenesis of secretory pathway proteins, including proteins localized to the ER, Golgi, lysosomes, intracellular vesicles, plasma membrane, and extracellular compartments. Proteins within the secretory pathway contain a high abundance of disulfide bonds to protect...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b01014

    authors: Bechtel TJ,Li C,Kisty EA,Maurais AJ,Weerapana E

    更新日期:2020-02-21 00:00:00

  • pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS.

    abstract::Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene ex...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00168

    authors: Deochand DK,Meariman JK,Grove A

    更新日期:2016-07-15 00:00:00

  • Mad2 Inhibitor-1 (M2I-1): A Small Molecule Protein-Protein Interaction Inhibitor Targeting the Mitotic Spindle Assembly Checkpoint.

    abstract::The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if correct...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00121

    authors: Kastl J,Braun J,Prestel A,Möller HM,Huhn T,Mayer TU

    更新日期:2015-07-17 00:00:00

  • Structure-based design of an organoruthenium phosphatidyl-inositol-3-kinase inhibitor reveals a switch governing lipid kinase potency and selectivity.

    abstract::Mutations that constitutively activate the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, including alterations in PI3K, PTEN, and AKT, are found in a variety of human cancers, implicating the PI3K lipid kinase as an attractive target for the development of therapeutic agents to treat cancer and other relate...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb800039y

    authors: Xie P,Williams DS,Atilla-Gokcumen GE,Milk L,Xiao M,Smalley KS,Herlyn M,Meggers E,Marmorstein R

    更新日期:2008-05-16 00:00:00

  • Mechanistic Insights into Taxadiene Epoxidation by Taxadiene-5α-Hydroxylase.

    abstract::The anticancer molecule taxol (Paclitaxel) stands as one of the most medically and economically important natural products. However, despite decades of extensive study, its biosynthesis remains poorly understood. Unpredictable behavior of the first oxygenation enzyme, taxadiene-5α-hydroxylase, which produces a range o...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00767

    authors: Edgar S,Zhou K,Qiao K,King JR,Simpson JH,Stephanopoulos G

    更新日期:2016-02-19 00:00:00

  • The N-Terminal Domain of NPHP1 Folds into a Monomeric Left-Handed Antiparallel Three-Stranded Coiled Coil with Anti-apoptotic Function.

    abstract::Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00582

    authors: Mannella V,Quilici G,Nigro EA,Lampis M,Minici C,Degano M,Boletta A,Musco G

    更新日期:2019-08-16 00:00:00

  • Heterologous Biosynthesis of Type II Polyketide Products Using E. coli.

    abstract::The heterologous biosynthesis of complex natural products has enabled access to polyketide, nonribosomal peptide, isoprenoid, and other compounds with wide-spanning societal value. Though several surrogate host systems exist, Escherichia coli is often a preferred choice due to its rapid growth kinetics and extensive m...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00827

    authors: Liu X,Hua K,Liu D,Wu ZL,Wang Y,Zhang H,Deng Z,Pfeifer BA,Jiang M

    更新日期:2020-05-15 00:00:00

  • CB-6644 Is a Selective Inhibitor of the RUVBL1/2 Complex with Anticancer Activity.

    abstract::RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor pro...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b00904

    authors: Assimon VA,Tang Y,Vargas JD,Lee GJ,Wu ZY,Lou K,Yao B,Menon MK,Pios A,Perez KC,Madriaga A,Buchowiecki PK,Rolfe M,Shawver L,Jiao X,Le Moigne R,Zhou HJ,Anderson DJ

    更新日期:2019-02-15 00:00:00