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 ResearchMeSH KeywordsDNA DamageEscherichia coliEscherichia coli ProteinsFatty AcidsHumansLactamsMolecular StructurePeptidesPolyketidesConceptsFatty 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 coliSymptomsIBDStructure 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 cultureResiduesPathwayCleavageCellsStrandsGut
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 ResearchMeSH KeywordsDNA AdductsEscherichia coliEscherichia coli ProteinsIsotope LabelingMutationPeptide HydrolasesPeptidesPolyketidesProtein ConformationSecondary MetabolismTandem Mass SpectrometryConceptsColibactin-producing bacteriaCell biology dataColibactin gene clusterCombination of geneticsComplex secondary metabolitesGene clusterIsotope labelingSecondary metabolitesBiology dataColibactinHuman gutTandem mass spectrometryBacteriaPhysiological effectsMass spectrometryStructure elucidationGutGeneticsDNAEnzymeChemical synthesisEscherichiaElucidationMetabolitesLabeling
2016
A Mechanistic Model for Colibactin-Induced Genotoxicity
Healy AR, Nikolayevskiy H, Patel JR, Crawford JM, Herzon SB. A Mechanistic Model for Colibactin-Induced Genotoxicity. Journal Of The American Chemical Society 2016, 138: 15563-15570. PMID: 27934011, PMCID: PMC5359767, DOI: 10.1021/jacs.6b10354.Peer-Reviewed Original ResearchMeSH KeywordsBiological ProductsDNA CleavageEscherichia coliEscherichia coli ProteinsMolecular StructureMultigene FamilyMutagensPeptide HydrolasesPeptidesPhenotypePolyketidesConceptsGene clusterE. coliDNA double-strand breaksDouble-strand breaksProbiotic Nissle 1917Clb gene clusterEukaryotic cellsCertain commensalDNA bindingProbiotic E. coliDisparate phenotypesPrecolibactinsAlkylate DNAColibactinIsolation effortsFermentation productsColiDNA alkylationDNANissle 1917Mechanistic modelSide chainsNatural productsMetabolite structuresEfficient DNA alkylation