2024
Bacterial small molecule metabolites implicated in gastrointestinal cancer development
Turocy T, Crawford J. Bacterial small molecule metabolites implicated in gastrointestinal cancer development. Nature Reviews Microbiology 2024, 1-16. PMID: 39375475, DOI: 10.1038/s41579-024-01103-4.Peer-Reviewed Original ResearchSmall molecule metabolitesGastrointestinal cancer developmentAssociated with cancer progressionHost–microorganism interactionsGastrointestinal cancerCancer riskCancer developmentCancer progressionCancerTherapeutic interventionsMicrobiome membersHuman microbiomeBacterial speciesGlobal causeMolecular mechanismsMetabolitesRisk
2022
Cellular Stress-Induced Metabolites in Escherichia coli
Gatsios A, Kim C, York A, Flavell R, Crawford J. Cellular Stress-Induced Metabolites in Escherichia coli. Journal Of Natural Products 2022, 85: 2626-2640. PMID: 36346625, PMCID: PMC9949963, DOI: 10.1021/acs.jnatprod.2c00706.Peer-Reviewed Original ResearchCommensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 2022, 378: eabm3233. PMID: 36302024, PMCID: PMC9993714, DOI: 10.1126/science.abm3233.Peer-Reviewed Original ResearchConceptsColorectal cancerInflammatory bowel disease patientsBowel disease patientsInflammatory bowel diseaseIndigenous gut microbesBowel diseaseDisease patientsCommensal microbiotaDNA damageColon tumorigenesisElicit DNA damageGut microbesGenotoxic metabolitesGut commensalsMorganella morganiiPatientsGenotoxic chemicalsDiseaseMicrobiotaMetabolitesGenotoxicityCancerMiceFull spectrumDamage
2021
Escherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis
Kim CS, Turocy T, Moon G, Shine EE, Crawford JM. Escherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis. Organic Letters 2021, 23: 6895-6899. PMID: 34406772, PMCID: PMC10577019, DOI: 10.1021/acs.orglett.1c02461.Peer-Reviewed Original ResearchConceptsFatty acid biosynthesisAcid biosynthesisHybrid polyketide-nonribosomal peptideNuclear magnetic resonance spectroscopyΓ-lactam derivativesUnknown biological activityBiosynthetic logicMagnetic resonance spectroscopyCancer initiationColorectal cancer initiationStereochemical analysisΓ-lactamsColibactinResonance spectroscopyDiverse collectionBiosynthesisBiological activityAbundant metabolitesPathwayRelated metabolitesRelated structuresMetabolitesLociProteinSpectroscopy
2020
Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli
Park HB, Wei Z, Oh J, Xu H, Kim CS, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford JM. Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli. Nature Microbiology 2020, 5: 1319-1329. PMID: 32719505, PMCID: PMC7581551, DOI: 10.1038/s41564-020-0763-4.Peer-Reviewed Original ResearchConceptsAnti-inflammatory interleukin-10Colitis mouse modelInflammatory bowel diseaseColitis symptomsBowel diseaseInterleukin-10Immunological markersPathogenic roleImmunomodulatory metabolitesImmunomodulatory phenotypeGastrointestinal tractMouse modelImmunological activityPrimary human tissuesDrug stressSubinhibitory levelsHuman tissuesEnvironmental isolatesCertain strainsMetabolic pathwaysMetabolitesPatientsEscherichia coliSymptomsIBDCellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli
Kim CS, Li JH, Barco B, Park HB, Gatsios A, Damania A, Wang R, Wyche TP, Piizzi G, Clay NK, Crawford JM. Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli. Cell Chemical Biology 2020, 27: 698-707.e7. PMID: 32243812, PMCID: PMC7306003, DOI: 10.1016/j.chembiol.2020.03.003.Peer-Reviewed Original ResearchConceptsPlant-pathogen defense responsesPlant innate immune responsesPathogen defense responsesSmall molecule signalsEscherichia coliPersister cell formationStress-induced metabolitesPrimary human tissuesDefense responsesRedox stressorsInnate immune responseDistinct immunological responsesMolecule signalsMolecular studiesCell formationColiBacterial metabolitesDefensive responsesSmall moleculesPlantsHuman tissuesImmune responseImmunological responseInfection modelMetabolitesCharacterization of Autoinducer‑3 Structure and Biosynthesis in E. coli
Kim CS, Gatsios A, Cuesta S, Lam YC, Wei Z, Chen H, Russell RM, Shine EE, Wang R, Wyche TP, Piizzi G, Flavell RA, Palm NW, Sperandio V, Crawford JM. Characterization of Autoinducer‑3 Structure and Biosynthesis in E. coli. ACS Central Science 2020, 6: 197-206. PMID: 32123737, PMCID: PMC7047286, DOI: 10.1021/acscentsci.9b01076.Peer-Reviewed Original ResearchAutoinducer-3Population-level phenotypesDiverse biological rolesGram-positive bacterial pathogensPrimary human tissuesModel organismsQuorum sensingMolecular foundationBiological roleCommon inhabitantsVariety of GramHuman microbiotaVirulence genesBacterial pathogensE. coliBiochemical originBiosynthesisHuman tissuesUnknown structureSynthetase reactionGenesOrganismsBiologyMetabolitesEnterohemorrhagic
2019
Structure elucidation of colibactin and its DNA cross-links
Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, Shine EE, Wang W, Herzon SB, Crawford JM. Structure elucidation of colibactin and its DNA cross-links. Science 2019, 365 PMID: 31395743, PMCID: PMC6820679, DOI: 10.1126/science.aax2685.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaCell biology dataColibactin gene clusterCombination of geneticsComplex secondary metabolitesGene clusterIsotope labelingSecondary metabolitesBiology dataColibactinHuman gutTandem mass spectrometryBacteriaPhysiological effectsMass spectrometryStructure elucidationGutGeneticsDNAEnzymeChemical synthesisEscherichiaElucidationMetabolitesLabelingBright Green Biofluorescence in Sharks Derives from Bromo-Kynurenine Metabolism
Park HB, Lam YC, Gaffney JP, Weaver JC, Krivoshik SR, Hamchand R, Pieribone V, Gruber DF, Crawford JM. Bright Green Biofluorescence in Sharks Derives from Bromo-Kynurenine Metabolism. IScience 2019, 19: 1291-1336. PMID: 31402257, PMCID: PMC6831821, DOI: 10.1016/j.isci.2019.07.019.Peer-Reviewed Original ResearchGreen fluorescent proteinGFP-like proteinsSpecies of sharksAcid-binding proteinFluorescence microscopy studiesFatty acid-binding proteinUndescribed groupSmall molecule metabolitesLuminescent phenotypeFluorescent proteinProteinMicrobial infectionsBiofluorescenceMarine environmentSharksSmall moleculesStructural detailsDiscovery of metabolitesWidespread natureCentral nervous systemNervous systemSpectral characterizationSpeciesMetabolitesDiversityA Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology
Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM, Palm NW. A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell 2019, 177: 1217-1231.e18. PMID: 31006530, PMCID: PMC6536006, DOI: 10.1016/j.cell.2019.03.036.Peer-Reviewed Original ResearchConceptsHost physiologyBioactive microbial metabolitesHuman gut bacteriaHost sensingProlific producersG proteinsGut microbiota metabolitesBlood-brain barrierL-PheMicrobial metabolitesOrphan GPCRsGut bacteriaColonic motilityInhibitor administrationMicrobiota metabolitesIntestinal microbiotaSmall moleculesDietary histidineBacteriaPhysiologyMicrobiota metabolomeMetabolitesGPR97Orthogonal approachGPCRs
2017
Acyl Histidines: New N‐Acyl Amides from Legionella pneumophila
Tørring T, Shames SR, Cho W, Roy CR, Crawford JM. Acyl Histidines: New N‐Acyl Amides from Legionella pneumophila. ChemBioChem 2017, 18: 638-646. PMID: 28116768, PMCID: PMC5546091, DOI: 10.1002/cbic.201600618.Peer-Reviewed Original ResearchConceptsBiosynthetic gene clusterOrphan biosynthetic gene clustersPathogen-insect interactionsAmino acid-derived metabolitesLegionella pneumophilaOrphan pathwaysBiosynthetic genesVariety of protozoanGene clusterN-acyl amidesMolecular networkingHuman macrophagesDistinct groupsPneumophilaCausative agentPathwayMetabolitesHistidine metabolitesNew N-acylGenesLegionnaires' diseaseAmoebaeProtozoaMacrophagesPathogens
2016
Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens
Park HB, Crawford JM. Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens. The Journal Of Antibiotics 2016, 69: 616-621. PMID: 27353165, PMCID: PMC5003743, DOI: 10.1038/ja.2016.79.Peer-Reviewed Original ResearchConceptsSpecialized metabolitesNew specialized metabolitesMutualistic associationAmino acid levelsInsect pathogenesisInsect preyGalleria mellonella larvaePhotorhabdus genusP. luminescensPhenotypic variationFamilies HeterorhabditidaeNematode developmentEntomopathogenic bacteriumProtease inhibitory activityFree amino acid levelsRich mediumAmino acidsMellonella larvaePhenotypic variantsMarfey's analysisPhotorhabdusCirculatory fluidCulture extractsMetabolitesHeterorhabditidaeLinking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking
Trautman EP, Crawford JM. Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking. Current Topics In Medicinal Chemistry 2016, 16: 1705-1716. PMID: 26456470, PMCID: PMC5055756, DOI: 10.2174/1568026616666151012111046.Peer-Reviewed Original ResearchConceptsBiosynthetic gene clusterGene clusterMicrobial biosynthetic gene clustersMetabolic pathwaysGenome sequence informationSecondary metabolic pathwaysMolecular networkingHuman-microbe interactionsNew metabolic pathwaysComplex metabolomeSmall moleculesBiosynthetic logicActive small moleculesFunctional characterizationBioinformatics predictionSequence informationSmall molecule metabolitesHuman microbiomeExperimental structural characterizationGut bacteriaPathwayNatural productsMetabolitesPharmacological potentialAvailable databases