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 ResearchMeSH KeywordsBacteriaBiosynthetic PathwaysEukaryotaGenetic EngineeringHost Microbial InteractionsHumansMetabolomicsMicrobiotaSynthetic BiologyConceptsSynthetic 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
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 ResearchMeSH KeywordsAmino AcidsBiosynthetic PathwaysCarbohydratesGlycopeptidesMultigene FamilyPeptide FragmentsPeptide SynthasesPhotorhabdusConceptsHypothetical 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
Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster
Park HB, Perez CE, Barber KW, Rinehart J, Crawford JM. Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster. ELife 2017, 6: e25229. PMID: 28431213, PMCID: PMC5384830, DOI: 10.7554/elife.25229.Peer-Reviewed Original ResearchMeSH KeywordsBiosynthetic PathwaysComputational BiologyGene DeletionMagnetic Resonance SpectroscopyMultigene FamilyPeptide SynthasesPhotorhabdusProteomicsPteridinesConceptsBiosynthetic gene clusterNonribosomal peptide synthetaseGene clusterPeptide synthetaseGenome synteny analysisHybrid nonribosomal peptide synthetaseSecondary metabolic enzymesQuantitative proteomic analysisExtensive gene deletionsRedox-active cofactorsSynteny analysisMutualistic roleGenome miningBiosynthetic machineryPhenotypic variationBiosynthetic potentialNonribosomal peptidesProteomic analysisQuorum sensingGenetic lociMetabolic enzymesAcyl side chainPhenotypic variantsGene deletionDistinct classes
2016
Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking
Trautman EP, Crawford JM. Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking. Current Topics In Medicinal Chemistry 2016, 16: 1705-1716. PMID: 26456470, PMCID: PMC5055756, DOI: 10.2174/1568026616666151012111046.Peer-Reviewed Original ResearchMeSH KeywordsBiological ProductsBiosynthetic PathwaysComputational BiologyHumansMetabolic Networks and PathwaysMicrobiotaMultigene FamilyConceptsBiosynthetic gene clusterGene clusterMicrobial biosynthetic gene clustersMetabolic pathwaysGenome sequence informationSecondary metabolic pathwaysMolecular networkingHuman-microbe interactionsNew metabolic pathwaysComplex metabolomeSmall moleculesBiosynthetic logicActive small moleculesFunctional characterizationBioinformatics predictionSequence informationSmall molecule metabolitesHuman microbiomeExperimental structural characterizationGut bacteriaPathwayNatural productsMetabolitesPharmacological potentialAvailable databases
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
Merging 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 ResearchMeSH KeywordsBiological ProductsBiosynthetic PathwaysEcological and Environmental PhenomenaEnterobacteriaceaeGenome, BacterialPhotorhabdusSecondary MetabolismSymbiosisConceptsBacterial 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
2012
Microbial genome mining answers longstanding biosynthetic questions
Crawford JM, Clardy J. Microbial genome mining answers longstanding biosynthetic questions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 7589-7590. PMID: 22550177, PMCID: PMC3356616, DOI: 10.1073/pnas.1205361109.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 patternsPolyketidesAbsence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures
Ehrlich KC, Chang P, Scharfenstein LL, Cary JW, Crawford JM, Townsend CA. Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures. FEMS Microbiology Letters 2010, 305: 65-70. PMID: 20158523, PMCID: PMC2891446, DOI: 10.1111/j.1574-6968.2010.01914.x.Peer-Reviewed Original ResearchMeSH KeywordsAflatoxinsAlcohol DehydrogenaseAspergillus flavusBiosynthetic PathwaysFungal ProteinsGene Knockout TechniquesGenes, FungalMultigene FamilyOxidation-ReductionConceptsBiosynthetic gene clusterAflatoxin biosynthesis genesCytochrome P450 monooxygenaseAflatoxin biosynthetic gene clusterWild-type A. flavusBiosynthesis genesGene clusterP450 monooxygenaseAflatoxin biosynthesisCarcinogenic aflatoxinsAccumulation of aflatoxinBiosynthesisA. flavusMinor toxinsO-methylsterigmatocystinAspergillus speciesFinal stepAspergillus flavusNew metabolitesQuantities of aflatoxinElevated quantitiesMutantsAccumulationFlavusGenes