2024
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Hamchand R, Wang K, Song D, Palm N, Crawford J. Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca. Nature Communications 2024, 15: 8902. PMID: 39406708, PMCID: PMC11480411, DOI: 10.1038/s41467-024-53185-6.Peer-Reviewed Original ResearchConceptsK. oxytocaGeneral carbohydrate metabolismVirulence factor productionPLP-dependent enzymesAssociated with gutEnterobactin biosynthesisAutoinducer signalBacterial virulenceKlebsiella oxytocaSpecific carbohydratesHost immune responseCarbohydrate metabolismAutoinducerMolecular signalsVirulenceHistamine receptor H4BiosynthesisHost signalAcquisition responsesProtease inhibitorsPathwayHostLung pathologyLung isolationImmune response
2022
Cross-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
2019
A 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
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 ResearchSecondary Metabolic Pathway-Targeted Metabolomics
Vizcaino MI, Crawford JM. Secondary Metabolic Pathway-Targeted Metabolomics. Methods In Molecular Biology 2016, 1401: 175-195. PMID: 26831709, PMCID: PMC5049693, DOI: 10.1007/978-1-4939-3375-4_12.Peer-Reviewed Original ResearchConceptsHigh-resolution mass spectrometryNovel natural product discoveryIsotopic labelingNatural product discovery effortsMicrobial natural product biosynthesisOrphan biosynthetic pathwaysComplex organic mixturesGlobal Natural Products Social Molecular Networking (GNPS) platformNatural product discoveryMS/MS acquisitionNatural product biosynthesisAnalytes of interestMS data acquisitionMS/MS data acquisitionNatural product extractionOrganic mixturesMolecular networkingNatural productsChemometric platformProduct discoveryMass spectrometryProduct biosynthesisMS acquisitionLiquid chromatographyMethod development
2011
Bacterial symbionts and natural products
Crawford JM, Clardy J. Bacterial symbionts and natural products. Chemical Communications 2011, 47: 7559-7566. PMID: 21594283, PMCID: PMC3174269, DOI: 10.1039/c1cc11574j.Peer-Reviewed Original Research
2010
New insights into the formation of fungal aromatic polyketides
Crawford JM, Townsend CA. New insights into the formation of fungal aromatic polyketides. Nature Reviews Microbiology 2010, 8: 879-889. PMID: 21079635, PMCID: PMC3181163, DOI: 10.1038/nrmicro2465.Peer-Reviewed Original ResearchConceptsAromatic polyketide biosynthesisPolyketide synthasesStarter unitAromatic polyketidesNR-PKSsAcyl carrier protein domainIterative polyketide synthasesProduct template (PT) domainsAcyl-CoA poolSingle genomeProduct releaseKetosynthase domainCorrect substrateProtein domainsSubsequent product releaseBiosynthesis systemTemplate domainFilamentous fungiUnknown functionEnzyme structureDiverse familySynthesis pathwayKey cyclizationCyclization patternsPolyketides