2024
Selective utilization of glucose metabolism guides mammalian gastrulation
Cao D, Bergmann J, Zhong L, Hemalatha A, Dingare C, Jensen T, Cox A, Greco V, Steventon B, Sozen B. Selective utilization of glucose metabolism guides mammalian gastrulation. Nature 2024, 634: 919-928. PMID: 39415005, PMCID: PMC11499262, DOI: 10.1038/s41586-024-08044-1.Peer-Reviewed Original ResearchConceptsCellular metabolismMammalian gastrulationHexosamine biosynthetic pathwayTranscription factor networksCellular signaling pathwaysSignaling morphogensGlucose metabolismCellular programmeBiosynthetic pathwayFate acquisitionCell fateHousekeeping natureGenetic mechanismsMesoderm migrationFactor networksERK activationExpression patternsSignaling pathwayDevelopmental processesStem cell modelCell typesSpecialized functionsDevelopmental contextMammalian embryosMouse embryosAcatulides A-G, neuroprotective macrolides from Acaulium album H-JQSF
Tong Z, Wang T, Yang P, Sun J, Zhang C, Khan S, Wang X, Jiao R, Ge H, Zhuang W, Hu G, Tan R. Acatulides A-G, neuroprotective macrolides from Acaulium album H-JQSF. Chinese Chemical Letters 2024, 35: 108488. DOI: 10.1016/j.cclet.2023.108488.Peer-Reviewed Original Research
2023
Recoding UAG to selenocysteine in Saccharomyces cerevisiae
Hoffman K, Chung C, Mukai T, Krahn N, Jiang H, Balasuriya N, O'Donoghue P, Söll D. Recoding UAG to selenocysteine in Saccharomyces cerevisiae. RNA 2023, 29: 1400-1410. PMID: 37279998, PMCID: PMC10573291, DOI: 10.1261/rna.079658.123.Peer-Reviewed Original ResearchConceptsSelenoprotein productionYeast expression systemSeryl-tRNA synthetaseSite-specific incorporationEukaryotic relativesKingdom FungiSelenocysteine synthaseSelenophosphate synthetaseBiosynthesis pathwayEukaryotic selenoproteinsMetabolic engineeringBiosynthetic pathwayPathway componentsExpression systemReductase enzymeTRNASaccharomycesYeastTranslation componentsSpecific sitesFacile productionUnique chemicalSynthetasePathwayFirst demonstration
2022
A microbial transporter of the dietary antioxidant ergothioneine
Dumitrescu D, Gordon E, Kovalyova Y, Seminara A, Duncan-Lowey B, Forster E, Zhou W, Booth C, Shen A, Kranzusch P, Hatzios S. A microbial transporter of the dietary antioxidant ergothioneine. Cell 2022, 185: 4526-4540.e18. PMID: 36347253, PMCID: PMC9691600, DOI: 10.1016/j.cell.2022.10.008.Peer-Reviewed Original ResearchConceptsInter-kingdom competitionHost-associated microbesIntracellular redox homeostasisGastric pathogen Helicobacter pyloriPathogen Helicobacter pyloriRedox regulationSmall molecule antioxidantsRedox homeostasisBiosynthetic pathwayColonization advantageUnappreciated mechanismLMW thiolsHost environmentHuman faecal bacteriaWeight thiolsCertain microorganismsAntioxidant ergothioneineGastrointestinal microbesMetabolite trimethylamine N-oxideMicrobesMillimolar levelsHuman tissuesErgothioneineTrimethylamine N-oxideFecal bacteriaCell-specific bioorthogonal tagging of glycoproteins
Cioce A, Calle B, Rizou T, Lowery SC, Bridgeman VL, Mahoney KE, Marchesi A, Bineva-Todd G, Flynn H, Li Z, Tastan OY, Roustan C, Soro-Barrio P, Rafiee MR, Garza-Garcia A, Antonopoulos A, Wood TM, Keenan T, Both P, Huang K, Parmeggian F, Snijders AP, Skehel M, Kjær S, Fascione MA, Bertozzi CR, Haslam SM, Flitsch SL, Malaker SA, Malanchi I, Schumann B. Cell-specific bioorthogonal tagging of glycoproteins. Nature Communications 2022, 13: 6237. PMID: 36284108, PMCID: PMC9596482, DOI: 10.1038/s41467-022-33854-0.Peer-Reviewed Original ResearchConceptsMass spectrometry glycoproteomicsArtificial biosynthetic pathwayTumor-derived cell linesCellular model systemNon-transfected cellsCellular functionsProtein glycosylationBiosynthetic pathwayProteome analysisGlycosylation sitesBioorthogonal tagsCancer developmentCell linesModel systemImportant modulatorIntricate interactionsCo-culture modelGlycoproteinCellsGlycoprotein expressionMouse modelGlycoproteomeGlycosylationTaggingMonocultureTranscriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis
Hendrickson EL, Bor B, Kerns KA, Lamont EI, Chang Y, Liu J, Cen L, Schulte F, Hardt M, Shi W, He X, McLean JS. Transcriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis. Journal Of Bacteriology 2022, 204: e00112-22. PMID: 35975994, PMCID: PMC9487520, DOI: 10.1128/jb.00112-22.Peer-Reviewed Original ResearchConceptsCandidate Phyla RadiationEstablishment of symbiosisStable symbiosisStress-related genesGene expressionReduced genomePeptidoglycan biosynthesisHost bacteriaHuman microbiomeBiosynthesis gene expressionMonophyletic radiationCell sizeEffector genesPartitioning genesObligate parasitesUnique organismsBiosynthetic pathwayHigher gene expressionCell shapeTransporter geneCell wallObligate epibiontsLow expressionSymbiosisCell cycleCross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome
Patel JR, Oh J, Wang S, Crawford JM, Isaacs FJ. Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome. Cell 2022, 185: 1487-1505.e14. PMID: 35366417, PMCID: PMC10619838, DOI: 10.1016/j.cell.2022.03.008.Peer-Reviewed Original ResearchConceptsSynthetic genetic elementsGenetic elementsBiosynthetic gene clusterCross-species expressionCross-species interactionsDiverse organismsGene clusterBiosynthetic machineryHeterologous expressionRegulatory regionsTRNA synthetasesBiosynthetic pathwayNative contextTranslational activityBiosynthetic capacityHuman microbiomeMetabolic capacityPositive bacteriaSmall moleculesExpressionPathwayValuable compoundsLactobacillus inersEukaryotesSynthetases
2021
A Summary on Up-To-Date Research on Fungal Siderophores on Disease, Treatment and Pathogenicity Based on Text Mining, Bioinformatics and Experts’ Opinion
Prabahar A, Shanmugam L, Jose M, Radhakrishnan K, Raja K. A Summary on Up-To-Date Research on Fungal Siderophores on Disease, Treatment and Pathogenicity Based on Text Mining, Bioinformatics and Experts’ Opinion. Fungal Biology 2021, 187-210. DOI: 10.1007/978-3-030-53077-8_12.Peer-Reviewed Original ResearchSiderophore biosynthetic pathwaysFungal siderophoresBiosynthetic pathwayFungal diseasesTreatment of life-threatening infectionsIron acquisitionBioinformatics approachManual curationInfluence of siderophoresSiderophoreComprehensive collection of informationLife-threatening infectionsProtein targetsBacterial siderophoresFungiBioinformaticsTherapeutic targetComprehensive collectionPathwayAspergillosisFungalGenesPathogensCandidiasisProtein
2020
Structure and bioactivity of colibactin
Wernke KM, Xue M, Tirla A, Kim CS, Crawford JM, Herzon SB. Structure and bioactivity of colibactin. Bioorganic & Medicinal Chemistry Letters 2020, 30: 127280. PMID: 32527463, PMCID: PMC7309967, DOI: 10.1016/j.bmcl.2020.127280.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaStrands of DNABiosynthetic pathwaySecondary metabolitesColibactinMolecular-level explanationHuman gutAdenine residuesCell contactElectrophilic CyclopropanesCertain strainsBacteriaGenotoxic effectsHeterodimersDNABacterial cultureResiduesPathwayCleavageCellsStrandsGutBump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells
Schumann B, Malaker SA, Wisnovsky SP, Debets MF, Agbay AJ, Fernandez D, Wagner LJS, Lin L, Li Z, Choi J, Fox DM, Peh J, Gray MA, Pedram K, Kohler JJ, Mrksich M, Bertozzi CR. Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells. Molecular Cell 2020, 78: 824-834.e15. PMID: 32325029, PMCID: PMC7276986, DOI: 10.1016/j.molcel.2020.03.030.Peer-Reviewed Original ResearchConceptsLiving cellsPolypeptide N-acetylgalactosaminyl transferasesCell surface glycomesEssential biological processesComplex biosynthetic machineryMajor physiological processesN-acetylgalactosaminyl transferaseBiosynthetic regulationBiosynthetic machineryGlycosyltransferase familyIndividual glycosyltransferasesProtein glycosylationPosttranslational modificationsGlycan fine structureBiosynthetic pathwayPhysiological contextBiological processesPhysiological processesGlycan structuresSpecific substratesGlycosyltransferasesChemical functionalityExperimental strategiesCellsBiosynthesis
2019
Characterization of a Hybrid Nonribosomal Peptide–Carbohydrate Biosynthetic Pathway in Photorhabdus luminescens
Perez CE, Crawford JM. Characterization of a Hybrid Nonribosomal Peptide–Carbohydrate Biosynthetic Pathway in Photorhabdus luminescens. Biochemistry 2019, 58: 1131-1140. PMID: 30694662, DOI: 10.1021/acs.biochem.8b01120.Peer-Reviewed Original ResearchConceptsHypothetical proteinsBiosynthetic pathwayNRPS machineryHybrid nonribosomal peptide synthetaseBacterial biosynthetic pathwaysStable isotope labelingNonribosomal peptide synthetaseProtein mass spectrometryEntomopathogen PhotorhabdusFascinating chemistryOrphan pathwaysCharacterization of oligosaccharidesAcetyl-glucosamine moietyProduction of metabolitesGenomic islandsGlycoamino acidsNovel chemistryGene clusterHeterologous expressionProtein biochemistryPeptide synthetaseBiological functionsGenome sequencingMass spectrometryIsotope labeling
2018
Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
Orchard RC, Wilen CB, Virgin HW. Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection. Nature Microbiology 2018, 3: 1109-1114. PMID: 30127493, PMCID: PMC6158067, DOI: 10.1038/s41564-018-0221-8.Peer-Reviewed Original ResearchConceptsSerine palmitoyltransferase complexSphingolipid biosynthesisCellular susceptibilityConformational changesLipid biosynthetic enzymesDe novo sphingolipid biosynthesisHost cellular receptorsSerine palmitoyltransferase activityBiosynthetic enzymesBiosynthetic pathwayMurine norovirus infectionMurine norovirusCD300lfCell surfaceBiosynthesisUnappreciated connectionCellular receptorsExtracellular ceramideReceptor conformationViral infectionSurface expressionTarget cell surfaceViral bindingPalmitoyltransferase activityReceptorsThe Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut
Schofield WB, Zimmermann-Kogadeeva M, Zimmermann M, Barry NA, Goodman AL. The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut. Cell Host & Microbe 2018, 24: 120-132.e6. PMID: 30008292, PMCID: PMC6086485, DOI: 10.1016/j.chom.2018.06.002.Peer-Reviewed Original ResearchConceptsCarbon starvationStringent responseHuman gut bacterium Bacteroides thetaiotaomicronTricarboxylic acid cycle genesMultiple biosynthetic pathwaysCycle genesCentral metabolismMammalian gutTriggers accumulationBiosynthetic pathwayBacteroides thetaiotaomicronDeficient strainMetabolic regulatorAlpha-ketoglutarate supplementationStarvationAlpha-ketoglutarateC labelingCommensal bacteriaMetabolomic analysisGut microbiomeCommensal bacteriumThetaiotaomicronBacteriaPathwayGut65 Melanocyte Biology
Bolognia J, Orlow S. 65 Melanocyte Biology. 2018, 1075-1086.e1. DOI: 10.1016/b978-0-7020-6275-9.00065-9.Peer-Reviewed Original ResearchMelanin biosynthetic pathwayProduction of eumelaninMelanocortin 1 receptorBiosynthetic pathwayTransfer to keratinocytesPigment productionMelanin synthesisBrown-blackMelanocyte stimulating hormoneMelanosomesIntracytoplasmic organellesPheomelaninMelaninMelanocytesOrganellesEnzymeActivity of melanocytesPathwayBindingEumelaninNormal skin colorSkin colorTyrosinase
2017
Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway
Guntaka NS, Healy AR, Crawford JM, Herzon SB, Bruner SD. Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway. ACS Chemical Biology 2017, 12: 2598-2608. PMID: 28846367, PMCID: PMC5830302, DOI: 10.1021/acschembio.7b00479.Peer-Reviewed Original ResearchConceptsColibactin gene clusterÅ crystal structurePolyketide secondary metabolitesAcyl-thioester substratesColibactin biosynthesisGene clusterBiosynthetic pathwayAtypical roleGene productsBiochemical characterizationFunctional analysisSecondary metabolitesGreater catalytic efficiencyCancer formationColorectal cancer formationHuman gutSpecific functionsNovel insightsCarrier proteinThioesteraseGenetic deletionClbQColibactinCatalytic efficiencyPathwayLanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages
Araldi E, Fernández-Fuertes M, Canfrán-Duque A, Tang W, Cline GW, Madrigal-Matute J, Pober JS, Lasunción MA, Wu D, Fernández-Hernando C, Suárez Y. Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages. Cell Reports 2017, 19: 2743-2755. PMID: 28658622, PMCID: PMC5553565, DOI: 10.1016/j.celrep.2017.05.093.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Activator of transcriptionCholesterol biosynthetic pathwayTranscriptional repressionBiosynthetic pathwayLanosterol accumulationGene productsSterol intermediatesSignal transducerGene expressionSelective regulatorSTAT2 activationInnate immune responseType I interferonConditional disruptionCritical functionsMembrane fluidityROS productionMacrophage immunityListeria monocytogenes infectionResistance of miceMouse macrophagesInnate immunityI interferonCYP51A1
2016
Activating and Attenuating the Amicoumacin Antibiotics
Park HB, Perez CE, Perry EK, Crawford JM. Activating and Attenuating the Amicoumacin Antibiotics. Molecules 2016, 21: 824. PMID: 27347911, PMCID: PMC5055758, DOI: 10.3390/molecules21070824.Peer-Reviewed Original ResearchIdentification of a Chlamydomonas plastidial 2‐lysophosphatidic acid acyltransferase and its use to engineer microalgae with increased oil content
Yamaoka Y, Achard D, Jang S, Legéret B, Kamisuki S, Ko D, Schulz‐Raffelt M, Kim Y, Song W, Nishida I, Li‐Beisson Y, Lee Y. Identification of a Chlamydomonas plastidial 2‐lysophosphatidic acid acyltransferase and its use to engineer microalgae with increased oil content. Plant Biotechnology Journal 2016, 14: 2158-2167. PMID: 27133096, PMCID: PMC5096022, DOI: 10.1111/pbi.12572.Peer-Reviewed Original ResearchConceptsAcid acyltransferaseNitrogen-deficient conditionsOil contentPlastid membranesBiosynthetic pathwayStorage lipidsBiosynthetic processesReinhardtii cellsMicroalgal oil productionMolecular toolsSn-2 positionEnzyme assaysAlgal lipidsPhosphatidic acidCommon precursorMicroalgaeAcyltransferaseCoAMembranePlastidsLPAATChlamydomonasReinhardtiiLipidsGenes
2015
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell 2015, 163: 1716-1729. PMID: 26686653, PMCID: PMC4783382, DOI: 10.1016/j.cell.2015.11.045.Peer-Reviewed Original ResearchConceptsImport of cholesterolI interferonType I IFNsSTING-dependent mannerCholesterol biosynthetic pathwayI IFNsCombination of biosynthesisBiosynthetic fluxBiosynthetic pathwayLong-chain fatty acidsIsotope tracer analysisMetabolic shiftMetabolic pathwaysType I interferonCholesterol biosynthesisLipid requirementsChain fatty acidsInnate immunityBiosynthesisFatty acidsPool sizePathwayMechanistic studiesViral challengeFree cholesterolNeuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Haskins JW, Zhang S, Means RE, Kelleher JK, Cline GW, Canfrán-Duque A, Suárez Y, Stern DF. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science Signaling 2015, 8: ra111. PMID: 26535009, PMCID: PMC4666504, DOI: 10.1126/scisignal.aac5124.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNeuregulin-1Proto-Oncogene Proteins c-aktReceptor, ErbB-4Receptors, LDLSterol Regulatory Element Binding Protein 2TOR Serine-Threonine KinasesConceptsIntracellular domainEGFR family membersLow-density lipoprotein uptakeCholesterol biosynthesisSREBP target genesRapamycin complex 1ErbB4 intracellular domainSite-1 proteaseCholesterol biosynthesis genesSoluble intracellular domainCholesterol biosynthetic pathwayActivation of ErbB4Mammary epithelial cellsInhibition of AktSterol regulatory elementBiosynthesis genesLipoprotein uptakeRegulatory elementsBiosynthetic pathwayTarget genesDevelopmental processesMetabolic remodelingMature formNeuregulin-1Cellular membranes
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