当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > 2D NMR-based metabolomics uncovers interactions between conserved biochemical pathways in the model organism Caenorhabditis elegans.

2D NMR-based metabolomics uncovers interactions between conserved biochemical pathways in the model organism Caenorhabditis elegans.

Abstract：

:Ascarosides are small-molecule signals that play a central role in C. elegans biology, including dauer formation, aging, and social behaviors, but many aspects of their biosynthesis remain unknown. Using automated 2D NMR-based comparative metabolomics, we identified ascaroside ethanolamides as shunt metabolites in C. elegans mutants of daf-22, a gene with homology to mammalian 3-ketoacyl-CoA thiolases predicted to function in conserved peroxisomal lipid β-oxidation. Two groups of ethanolamides feature β-keto functionalization confirming the predicted role of daf-22 in ascaroside biosynthesis, whereas α-methyl substitution points to unexpected inclusion of methylmalonate at a late stage in the biosynthesis of long-chain fatty acids in C. elegans. We show that ascaroside ethanolamide formation in response to defects in daf-22 and other peroxisomal genes is associated with severe depletion of endocannabinoid pools. These results indicate unexpected interaction between peroxisomal lipid β-oxidation and the biosynthesis of endocannabinoids, which are major regulators of lifespan in C. elegans. Our study demonstrates the utility of unbiased comparative metabolomics for investigating biochemical networks in metazoans.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Izrayelit Y,Robinette SL,Bose N,von Reuss SH,Schroeder FC

doi

10.1021/cb3004644

subject

Has Abstract

pub_date

2013-02-15 00:00:00

pages

314-9

issue

2

eissn

1554-8929

issn

1554-8937

journal_volume

8

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.

    abstract：:The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00709

    authors： Heinzlmeir S,Kudlinzki D,Sreeramulu S,Klaeger S,Gande SL,Linhard V,Wilhelm M,Qiao H,Helm D,Ruprecht B,Saxena K,Médard G,Schwalbe H,Kuster B

    更新日期：2016-12-16 00:00:00

  • Identification of small molecule modulators of gene transcription with anticancer activity.

    abstract：:Epigenetic regulation of gene expression is essential in many biological processes, and its deregulation contributes to pathology including tumor formation. We used an image-based cell assay that measures the induction of a silenced GFP-estrogen receptor reporter to identify novel classes of small molecules involved i...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500532x

    authors： Tran TA,Wichterman-Kouznetsova J,Varghese D,Huang R,Huang W,Becker M,Austin CP,Inglese J,Johnson RL,Martinez ED

    更新日期：2014-11-21 00:00:00

  • Characterization of Sviceucin from Streptomyces Provides Insight into Enzyme Exchangeability and Disulfide Bond Formation in Lasso Peptides.

    abstract：:Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptide...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00584

    authors： Li Y,Ducasse R,Zirah S,Blond A,Goulard C,Lescop E,Giraud C,Hartke A,Guittet E,Pernodet JL,Rebuffat S

    更新日期：2015-11-20 00:00:00

  • Antiviral activity of an isatin derivative via induction of PERK-Nrf2-mediated suppression of cap-independent translation.

    abstract：:We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infe...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400775z

    authors： Zhang HM,Dai H,Hanson PJ,Li H,Guo H,Ye X,Hemida MG,Wang L,Tong Y,Qiu Y,Liu S,Wang F,Song F,Zhang B,Wang JG,Zhang LX,Yang D

    更新日期：2014-04-18 00:00:00

  • Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells.

    abstract：:Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling ide...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/acschembio.6b00766

    authors： Ward JA,McLellan L,Stockley M,Gibson KR,Whitlock GA,Knights C,Harrigan JA,Jacq X,Tate EW

    更新日期：2016-12-16 00:00:00

  • Engineered Flumazenil Recognition Site Provides Mechanistic Insight Governing Benzodiazepine Modulation in GABAA Receptors.

    abstract：:The anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic effects of benzodiazepine site ligands are mainly elicited by allosteric modulation of GABAA receptors via their extracellular αx+/γ2- ( x = 1, 2, 3, 5) interfaces. In addition, a low affinity binding site at the homologous α+/β- interfaces was rep...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00145

    authors： Siebert DCB,Bampali K,Puthenkalam R,Varagic Z,Sarto-Jackson I,Scholze P,Sieghart W,Mihovilovic MD,Schnürch M,Ernst M

    更新日期：2018-08-17 00:00:00

  • Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implications for antibiotic design.

    abstract：:Peptidoglycan glycosyltransferases (PGTs), enzymes that catalyze the formation of the glycan chains of the bacterial cell wall, have tremendous potential as antibiotic targets. The moenomycins, a potent family of natural product antibiotics, are the only known active site inhibitors of the PGTs and serve as blueprints...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb800078a

    authors： Yuan Y,Fuse S,Ostash B,Sliz P,Kahne D,Walker S

    更新日期：2008-07-18 00:00:00

  • First-in-class small molecule inhibitors of the single-strand DNA cytosine deaminase APOBEC3G.

    abstract：:APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput s...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200440y

    authors： Li M,Shandilya SM,Carpenter MA,Rathore A,Brown WL,Perkins AL,Harki DA,Solberg J,Hook DJ,Pandey KK,Parniak MA,Johnson JR,Krogan NJ,Somasundaran M,Ali A,Schiffer CA,Harris RS

    更新日期：2012-03-16 00:00:00

  • Discovery of a nitric oxide responsive quorum sensing circuit in Vibrio harveyi.

    abstract：:Bacteria use small molecules to assess the density and identity of nearby organisms and formulate a response. This process, called quorum sensing (QS), commonly regulates bioluminescence, biofilm formation, and virulence. Vibrio harveyi have three described QS circuits. Each involves the synthesis of a molecule that r...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300215t

    authors： Henares BM,Higgins KE,Boon EM

    更新日期：2012-08-17 00:00:00

  • A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.

    abstract：:Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb100195d

    authors： Nelson JW,Chamessian AG,McEnaney PJ,Murelli RP,Kazmierczak BI,Spiegel DA

    更新日期：2010-12-17 00:00:00

  • Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2).

    abstract：:Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceram...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00192

    authors： Charoenwattanasatien R,Pengthaisong S,Breen I,Mutoh R,Sansenya S,Hua Y,Tankrathok A,Wu L,Songsiriritthigul C,Tanaka H,Williams SJ,Davies GJ,Kurisu G,Cairns JR

    更新日期：2016-07-15 00:00:00

  • Profiling substrates of protein arginine N-methyltransferase 3 with S-adenosyl-L-methionine analogues.

    abstract：:Protein arginine N-methyltransferase 3 (PRMT3) belongs to the family of type I PRMTs and harbors the activity to use S-adenosyl-l-methionine (SAM) as a methyl-donor cofactor for protein arginine labeling. However, PRMT3's functions remain elusive with the lacked knowledge of its target scope in cellular settings. Insp...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb4008259

    authors： Guo H,Wang R,Zheng W,Chen Y,Blum G,Deng H,Luo M

    更新日期：2014-02-21 00:00:00

  • A Hydrogel-Microsphere Drug Delivery System That Supports Once-Monthly Administration of a GLP-1 Receptor Agonist.

    abstract：:We have developed a chemically controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00218

    authors： Schneider EL,Hearn BR,Pfaff SJ,Reid R,Parkes DG,Vrang N,Ashley GW,Santi DV

    更新日期：2017-08-18 00:00:00

  • Esterase-Triggered Self-Immolative Thiocarbamates Provide Insights into COS Cytotoxicity.

    abstract：:Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly conver...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/acschembio.8b00981

    authors： Levinn CM,Steiger AK,Pluth MD

    更新日期：2019-02-15 00:00:00

  • In vivo imaging of Caenorhabditis elegans glycans.

    abstract：:The nematode Caenorhabditis elegans is an excellent model organism for studies of glycan dynamics, a goal that requires tools for imaging glycans in vivo. Here we applied the bioorthogonal chemical reporter technique for the molecular imaging of mucin-type O-glycans in live C. elegans. We treated worms with azidosugar...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900254y

    authors： Laughlin ST,Bertozzi CR

    更新日期：2009-12-18 00:00:00

  • Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin.

    abstract：:Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involv...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00979

    authors： Cramer J,Krimmer SG,Fridh V,Wulsdorf T,Karlsson R,Heine A,Klebe G

    更新日期：2017-01-20 00:00:00

  • Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production.

    abstract：:The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their effi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00256

    authors： Poh WH,Barraud N,Guglielmo S,Lazzarato L,Rolando B,Fruttero R,Rice SA

    更新日期：2017-08-18 00:00:00

  • Discovery of small-molecule enhancers of reactive oxygen species that are nontoxic or cause genotype-selective cell death.

    abstract：:Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to ide...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300653v

    authors： Adams DJ,Boskovic ZV,Theriault JR,Wang AJ,Stern AM,Wagner BK,Shamji AF,Schreiber SL

    更新日期：2013-05-17 00:00:00

  • Engineering Intracellularly Retained Gaussia Luciferase Reporters for Improved Biosensing and Molecular Imaging Applications.

    abstract：:Gaussia luciferase (GLUC) is a bioluminescent reporter protein of increasing importance. As a secretory protein, it has increased sensitivity in vitro and in vivo (∼20 000-fold, and ∼1000-fold, respectively) over its competitor, secreted alkaline phosphatase. Unfortunately, this same advantageous secretory nature of G...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00454

    authors： Gaur S,Bhargava-Shah A,Hori S,Afjei R,Sekar TV,Gambhir SS,Massoud TF,Paulmurugan R

    更新日期：2017-09-15 00:00:00

  • Traceless labeling of glycoproteins and its application to the study of glycoprotein-protein interactions.

    abstract：:A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400631w

    authors： Yang YL,Lee YP,Yang YL,Lin PC

    更新日期：2014-02-21 00:00:00

  • Chemical probes of surface layer biogenesis in Clostridium difficile.

    abstract：:Clostridium difficile, a leading cause of hospital-acquired infection, possesses a dense surface layer (S-layer) that mediates host-pathogen interactions. The key structural components of the S-layer result from proteolytic cleavage of a precursor protein, SlpA, into high- and low-molecular-weight components. Here we ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb9002859

    authors： Dang TH,de la Riva L,Fagan RP,Storck EM,Heal WP,Janoir C,Fairweather NF,Tate EW

    更新日期：2010-03-19 00:00:00

  • Parietal Structures of Escherichia coli Can Impact the D-Cateslytin Antibacterial Activity.

    abstract：:Bacterial resistance to conventional antibiotics is of major concern. Antimicrobial peptides (AMPs) are considered excellent alternatives. Among them, D-cateslytin (D-Ctl, derivative of a host defense peptide) has shown high efficiency against a broad spectrum of bacteria. The first target of AMPs is the outer membran...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00622

    authors： Quilès F,Barth D,Peric O,Fantner GE,Francius G

    更新日期：2020-10-16 00:00:00

  • Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.

    abstract：:Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00715

    authors： Mitchell AC,Alford SC,Hunter SA,Kannan D,Parra Sperberg RA,Chang CH,Cochran JR

    更新日期：2018-01-19 00:00:00

  • Regioselective hydroxylation of trans-resveratrol via inhibition of tyrosinase from Streptomyces avermitilis MA4680.

    abstract：:Secreted tyrosinase from melanin-forming Streptomyces avermitilis MA4680 was involved in both ortho-hydroxylation and further oxidation of trans-resveratrol, leading to the formation of melanin. This finding was confirmed by constructing deletion mutants of melC(2) and melD(2) encoding extracellular and intracellular ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300222b

    authors： Lee N,Kim EJ,Kim BG

    更新日期：2012-10-19 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

  • Imaging the lipidome: omega-alkynyl fatty acids for detection and cellular visualization of lipid-modified proteins.

    abstract：:Fatty acylation or lipid modification of proteins controls their cellular activation and diverse roles in physiology. It mediates protein-protein and protein-membrane interactions and plays an important role in regulating cellular signaling pathways. Currently, there is need for visualizing lipid modifications of prot...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900085z

    authors： Hannoush RN,Arenas-Ramirez N

    更新日期：2009-07-17 00:00:00

  • Rational design of an auxin antagonist of the SCF(TIR1) auxin receptor complex.

    abstract：:The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary comple...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200404c

    authors： Hayashi K,Neve J,Hirose M,Kuboki A,Shimada Y,Kepinski S,Nozaki H

    更新日期：2012-03-16 00:00:00

  • A molecular-beacon-based screen for small molecule inhibitors of miRNA maturation.

    abstract：:miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have d...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300650y

    authors： Bose D,Jayaraj GG,Kumar S,Maiti S

    更新日期：2013-05-17 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

  • Diverse functional roles of reactive cysteines.

    abstract：:Cysteine residues on proteins play key roles in catalysis and regulation. These functional cysteines serve as active sites for nucleophilic and redox catalysis, sites of allosteric regulation, and metal-binding ligands on proteins from diverse classes including proteases, kinases, metabolic enzymes, and transcription ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb3005269

    authors： Pace NJ,Weerapana E

    更新日期：2013-02-15 00:00:00