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
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 arrayA community resource for paired genomic and metabolomic data mining
Schorn MA, Verhoeven S, Ridder L, Huber F, Acharya DD, Aksenov AA, Aleti G, Moghaddam JA, Aron AT, Aziz S, Bauermeister A, Bauman KD, Baunach M, Beemelmanns C, Beman JM, Berlanga-Clavero MV, Blacutt AA, Bode HB, Boullie A, Brejnrod A, Bugni TS, Calteau A, Cao L, Carrión VJ, Castelo-Branco R, Chanana S, Chase AB, Chevrette MG, Costa-Lotufo LV, Crawford JM, Currie CR, Cuypers B, Dang T, de Rond T, Demko AM, Dittmann E, Du C, Drozd C, Dujardin JC, Dutton RJ, Edlund A, Fewer DP, Garg N, Gauglitz JM, Gentry EC, Gerwick L, Glukhov E, Gross H, Gugger M, Guillén Matus DG, Helfrich EJN, Hempel BF, Hur JS, Iorio M, Jensen PR, Kang KB, Kaysser L, Kelleher NL, Kim CS, Kim KH, Koester I, König GM, Leao T, Lee SR, Lee YY, Li X, Little JC, Maloney KN, Männle D, Martin H. C, McAvoy AC, Metcalf WW, Mohimani H, Molina-Santiago C, Moore BS, Mullowney MW, Muskat M, Nothias LF, O’Neill E, Parkinson EI, Petras D, Piel J, Pierce EC, Pires K, Reher R, Romero D, Roper MC, Rust M, Saad H, Saenz C, Sanchez LM, Sørensen SJ, Sosio M, Süssmuth RD, Sweeney D, Tahlan K, Thomson RJ, Tobias NJ, Trindade-Silva AE, van Wezel GP, Wang M, Weldon KC, Zhang F, Ziemert N, Duncan KR, Crüsemann M, Rogers S, Dorrestein PC, Medema MH, van der Hooft JJJ. A community resource for paired genomic and metabolomic data mining. Nature Chemical Biology 2021, 17: 363-368. PMID: 33589842, PMCID: PMC7987574, DOI: 10.1038/s41589-020-00724-z.Peer-Reviewed Original Research
2017
Domain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis
Trautman EP, Healy AR, Shine EE, Herzon SB, Crawford JM. Domain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis. Journal Of The American Chemical Society 2017, 139: 4195-4201. PMID: 28240912, PMCID: PMC5831107, DOI: 10.1021/jacs.7b00659.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetasesPolyketide synthasesModular polyketide synthasesSite-directed mutagenesisCombination of genesCellular metabolic levelsColibactin biosynthesisMultidomain proteinsProtein domainsPeptide synthetasesCatalytic domainControl pathwaysProtein biochemicalPathway analysisCertain Escherichia coliComplete deletionHybrid pathwayEscherichia coliFunctional readoutBiosynthesisCatalytic mechanismCellular levelMetabolic levelPathwayGenes
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
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
2010
Regulating Alternative Lifestyles in Entomopathogenic Bacteria
Crawford JM, Kontnik R, Clardy J. Regulating Alternative Lifestyles in Entomopathogenic Bacteria. Current Biology 2010, 20: 69-74. PMID: 20022247, PMCID: PMC2821981, DOI: 10.1016/j.cub.2009.10.059.Peer-Reviewed Original ResearchConceptsAntibiotic productionMetabolic shiftNematode digestive tractBacterial proton motive forceBacterial metabolic regulationProton motive forceGenus PhotorhabdusTransporter PutPEntomopathogenic bacteriaInsect larvaeSmall moleculesInsecticidal toxinsNematode hostsInsect hemolymphBacterial pathwaysXenorhabdus nematophilaFungal competitorsDigestive tractL-prolineMetabolic regulationMotive forceHost environmentPhotorhabdusTT01Bacteria