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 array
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
2018
Functional Characterization of a Condensation Domain That Links Nonribosomal Peptide and Pteridine Biosynthetic Machineries in Photorhabdus luminescens
Perez CE, Park HB, Crawford JM. Functional Characterization of a Condensation Domain That Links Nonribosomal Peptide and Pteridine Biosynthetic Machineries in Photorhabdus luminescens. Biochemistry 2018, 57: 354-361. PMID: 29111689, DOI: 10.1021/acs.biochem.7b00863.Peer-Reviewed Original ResearchMeSH KeywordsChromatography, LiquidGenes, BacterialMass SpectrometryMultigene FamilyPeptide BiosynthesisPeptide SynthasesPhotorhabdusPteridinesConceptsNonribosomal peptide synthetasesCondensation domainMetabolic pathwaysSecondary metabolite biosynthesisSpecialized metabolic pathwaysBiosynthetic gene clusterNRPS condensation domainDistinct enzymatic systemsImportant small moleculesSecondary metabolite analysisCitric acid cycleMetabolite biosynthesisFunctional diversityGene clusterBiosynthetic machineryCellular redoxPeptide synthetasesNonribosomal peptidesBiosynthetic systemsQuorum sensingFunctional characterizationSolution studiesGenetic lociNatural productsBiochemical level
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 ResearchConceptsBiosynthetic 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 classesDomain-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 ResearchMeSH KeywordsEscherichia coliHeterocyclic CompoundsMetabolomicsMolecular ConformationPeptide SynthasesPeptidesPolyketide SynthasesPolyketidesConceptsNonribosomal 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
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 products
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