2021
A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides
Li JH, Cho W, Hamchand R, Oh J, Crawford JM. A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides. Journal Of Natural Products 2021, 84: 2692-2699. PMID: 34581573, PMCID: PMC9970011, DOI: 10.1021/acs.jnatprod.1c00573.Peer-Reviewed Original ResearchMeSH KeywordsCitrullineComputational BiologyLipopeptidesMetabolomicsMolecular StructurePeptide SynthasesXenorhabdusConceptsNonribosomal peptide synthetasePeptide synthetaseBiosynthetic gene clusterComparative genomic analysisFree-living infective juvenilesNRPS genesEffector proteinsInsect larvaeSpecialized metabolitesGene clusterMutualistic relationshipXenorhabdus bovieniiHeterologous expressionGenomic analysisRichest producersEntomopathogenic bacteriumSecondary metabolitesHost larvaeInfective juvenilesTermination domainInhibitor pathwayExogenous alcoholsLarvaeSpeciesComplex arrayEscherichia 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
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 cultureResiduesPathwayCleavageCellsStrandsGutDimeric Stilbene Antibiotics Target the Bacterial Cell Wall in Drug-Resistant Gram-Positive Pathogens
Goddard TN, Patel J, Park HB, Crawford JM. Dimeric Stilbene Antibiotics Target the Bacterial Cell Wall in Drug-Resistant Gram-Positive Pathogens. Biochemistry 2020, 59: 1966-1971. PMID: 32410442, PMCID: PMC10578317, DOI: 10.1021/acs.biochem.0c00213.Peer-Reviewed Original ResearchConceptsChemical complementation studiesBacterial cell wallMass spectrometry analysisLipid IILead compoundsMultidrug-resistant Gram-positive pathogensStilbene dimersCell wall precursorsSpectrometry analysisDrug-Resistant GramNew antimicrobial agentsGram-positive pathogensDimersNonlethal exposureAntibiotic targetsPositive pathogensDietary plantsAction studiesAntibiotic resistanceMode of actionAntimicrobial agentsLead dimerWall precursorsMonomersStrong activityA DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma
Adaku N, Park HB, Spakowicz DJ, Tiwari MK, Strobel SA, Crawford JM, Rogers FA. A DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma. Journal Of Natural Products 2020, 83: 1899-1908. PMID: 32407116, DOI: 10.1021/acs.jnatprod.0c00012.Peer-Reviewed Original ResearchConceptsPTEN-deficient glioblastoma cellsPTEN-deficient cancersTumor suppressor PTENImportant molecular toolPTEN-deficient glioblastomaInhibitor of DNAHuman cancer developmentDNA repair inhibitorsFungal endophytesBreak repairGenomic levelSuppressor PTENMolecular toolsEndophytic fungiSynthetic lethalityPTEN deficiencyGlioblastoma cellsRepair inhibitorsCancer developmentPTEN lossCurrent cancer treatmentsLarger patient populationTherapeutic leadsMedicinal plantsNew therapeutic leadsCellular 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 ResearchMeSH KeywordsAnimalsArabidopsisEscherichia coliFecesHumansIndolesMiceMice, Inbred C57BLMolecular StructureOxidative StressSignal TransductionUp-RegulationConceptsPlant-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 modelMetabolites
2019
An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype‑3 Agonists
Oh J, Kim NY, Chen H, Palm NW, Crawford JM. An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype‑3 Agonists. Journal Of The American Chemical Society 2019, 141: 16271-16278. PMID: 31537063, DOI: 10.1021/jacs.9b04183.Peer-Reviewed Original ResearchMeSH KeywordsCyanidesGlycopeptidesHEK293 CellsHumansModels, MolecularMolecular StructureReceptors, BombesinXenorhabdus
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 ResearchConceptsGene 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 alkylationActivating 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 ResearchConvergent and Modular Synthesis of Candidate Precolibactins. Structural Revision of Precolibactin A
Healy AR, Vizcaino MI, Crawford JM, Herzon SB. Convergent and Modular Synthesis of Candidate Precolibactins. Structural Revision of Precolibactin A. Journal Of The American Chemical Society 2016, 138: 5426-5432. PMID: 27025153, PMCID: PMC5049697, DOI: 10.1021/jacs.6b02276.Peer-Reviewed Original Research
2015
Lumiquinone A, an α‑Aminomalonate-Derived Aminobenzoquinone from Photorhabdus luminescens
Park HB, Crawford JM. Lumiquinone A, an α‑Aminomalonate-Derived Aminobenzoquinone from Photorhabdus luminescens. Journal Of Natural Products 2015, 78: 1437-1441. PMID: 25988621, PMCID: PMC5055755, DOI: 10.1021/np500974f.Peer-Reviewed Original Research
2014
Comparative Metabolomics and Structural Characterizations Illuminate Colibactin Pathway-Dependent Small Molecules
Vizcaino MI, Engel P, Trautman E, Crawford JM. Comparative Metabolomics and Structural Characterizations Illuminate Colibactin Pathway-Dependent Small Molecules. Journal Of The American Chemical Society 2014, 136: 9244-9247. PMID: 24932672, PMCID: PMC4091280, DOI: 10.1021/ja503450q.Peer-Reviewed Original ResearchConceptsReceptor antagonist activityE. coli Nissle 1917Coli Nissle 1917Ulcerative colitisInflammatory conditionsProbiotic E. coli Nissle 1917Human bowelPathogenic Escherichia coliAntagonist activityNissle 1917Growth inhibitoryCarcinogenic activityProbiotic activitySmall moleculesPathwayStructural network analysisColitisBowelComparative metabolomicsPersistence phenotypeMetabolomics
2011
NRPS Substrate Promiscuity Diversifies the Xenematides
Crawford JM, Portmann C, Kontnik R, Walsh CT, Clardy J. NRPS Substrate Promiscuity Diversifies the Xenematides. Organic Letters 2011, 13: 5144-5147. PMID: 21888371, PMCID: PMC3184645, DOI: 10.1021/ol2020237.Peer-Reviewed Original Research
2006
Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase
Crawford JM, Dancy BC, Hill EA, Udwary DW, Townsend CA. Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 16728-16733. PMID: 17071746, PMCID: PMC1636523, DOI: 10.1073/pnas.0604112103.Peer-Reviewed Original ResearchNew Images Evoke FAScinating Questions
Townsend CA, Crawford JM, Bililign T. New Images Evoke FAScinating Questions. Cell Chemical Biology 2006, 13: 349-351. PMID: 16632247, DOI: 10.1016/j.chembiol.2006.04.001.Peer-Reviewed Original Research