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
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 cultureResiduesPathwayCleavageCellsStrandsGut
2019
Characterization of a Hybrid Nonribosomal Peptide–Carbohydrate Biosynthetic Pathway in Photorhabdus luminescens
Perez CE, Crawford JM. Characterization of a Hybrid Nonribosomal Peptide–Carbohydrate Biosynthetic Pathway in Photorhabdus luminescens. Biochemistry 2019, 58: 1131-1140. PMID: 30694662, DOI: 10.1021/acs.biochem.8b01120.Peer-Reviewed Original ResearchConceptsHypothetical proteinsBiosynthetic pathwayNRPS machineryHybrid nonribosomal peptide synthetaseBacterial biosynthetic pathwaysStable isotope labelingNonribosomal peptide synthetaseProtein mass spectrometryEntomopathogen PhotorhabdusFascinating chemistryOrphan pathwaysCharacterization of oligosaccharidesAcetyl-glucosamine moietyProduction of metabolitesGenomic islandsGlycoamino acidsNovel chemistryGene clusterHeterologous expressionProtein biochemistryPeptide synthetaseBiological functionsGenome sequencingMass spectrometryIsotope labeling
2017
Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway
Guntaka NS, Healy AR, Crawford JM, Herzon SB, Bruner SD. Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway. ACS Chemical Biology 2017, 12: 2598-2608. PMID: 28846367, PMCID: PMC5830302, DOI: 10.1021/acschembio.7b00479.Peer-Reviewed Original ResearchConceptsColibactin gene clusterÅ crystal structurePolyketide secondary metabolitesAcyl-thioester substratesColibactin biosynthesisGene clusterBiosynthetic pathwayAtypical roleGene productsBiochemical characterizationFunctional analysisSecondary metabolitesGreater catalytic efficiencyCancer formationColorectal cancer formationHuman gutSpecific functionsNovel insightsCarrier proteinThioesteraseGenetic deletionClbQColibactinCatalytic efficiencyPathway
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 Research
2015
Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways
Engel P, Vizcaino MI, Crawford JM. Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways. Applied And Environmental Microbiology 2015, 81: 1502-1512. PMID: 25527542, PMCID: PMC4309719, DOI: 10.1128/aem.03283-14.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetaseBiosynthetic pathwayBacterial symbiontsGut symbiontsSecondary metabolitesEukaryotic cellsGenomic islandsBacterial gut symbiontDiverse symbiotic associationsDivergent variantsDNA damagePolyketide synthase pathwayE. coliComparative metabolomic analysisRelated secondary metabolitesPathway-dependent mannerSymbiotic associationGene clusterMicrobial interactionsBiosynthesis pathwayDistinct hostsPeptide synthetaseMammalian gutHoney beesSymbionts
2014
An Atypical Orphan Carbohydrate-NRPS Genomic Island Encodes a Novel Lytic Transglycosylase
Guo X, Crawford JM. An Atypical Orphan Carbohydrate-NRPS Genomic Island Encodes a Novel Lytic Transglycosylase. Cell Chemical Biology 2014, 21: 1271-1277. PMID: 25219963, PMCID: PMC4224617, DOI: 10.1016/j.chembiol.2014.07.025.Peer-Reviewed Original ResearchConceptsGenome synteny analysisSynteny analysisGenomic islandsLytic transglycosylaseNatural product gene clustersOrphan biosynthetic pathwaysGene deletion analysisGenome sequencing platformsRare structural featureBiochemical reconstructionHypothetical proteinsGene clusterAcetyl-glucosamine moietyHeterologous expressionDeletion analysisProtein homologyBiosynthetic pathwayIsland contentNew small moleculesSequencing platformsMetabolic chemistryTransglycosylasePathwaySmall moleculesNatural productsMerging chemical ecology with bacterial genome mining for secondary metabolite discovery
Vizcaino MI, Guo X, Crawford JM. Merging chemical ecology with bacterial genome mining for secondary metabolite discovery. Journal Of Industrial Microbiology & Biotechnology 2014, 41: 285-299. PMID: 24127069, PMCID: PMC3946945, DOI: 10.1007/s10295-013-1356-5.Peer-Reviewed Original ResearchConceptsBacterial genome miningOrphan biosynthetic pathwaysGenome miningChemical ecologyBiosynthetic pathwayBacterial secondary metabolismBiosynthetic gene clusterSecondary metabolic pathwaysSecondary metabolite discoveryLaboratory cultivation conditionsBioactive secondary metabolitesHost-bacteria interactionsMicrobial chemicalSymbiotic lifestylePhotorhabdus bacteriaSecondary metabolismGene clusterMutualistic relationshipSmall moleculesPhenotypic variationEcological nichesDiverse natural productsNatural productsPhysiological attributesSymbiotic system
2008
Acyl‐Carrier Protein–Phosphopantetheinyltransferase Partnerships in Fungal Fatty Acid Synthases
Crawford JM, Vagstad AL, Ehrlich KC, Udwary DW, Townsend CA. Acyl‐Carrier Protein–Phosphopantetheinyltransferase Partnerships in Fungal Fatty Acid Synthases. ChemBioChem 2008, 9: 1559-1563. PMID: 18551496, PMCID: PMC3189688, DOI: 10.1002/cbic.200700659.Peer-Reviewed Original Research