2018
Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria
Shine EE, Xue M, Patel JR, Healy AR, Surovtseva YV, Herzon SB, Crawford JM. Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria. ACS Chemical Biology 2018, 13: 3286-3293. PMID: 30403848, PMCID: PMC7001666, DOI: 10.1021/acschembio.8b00714.Peer-Reviewed Original ResearchConceptsHost bacteriaGenotoxic secondary metabolitesDNA double-strand breaksDNA interstrandSpecific protein domainsWild-type pathwayDouble-strand breaksFull molecular mechanismsCell culturesFamily of metabolitesHuman cell linesProtein domainsPresence of membranesModule skippingCellular phenotypesExtracellular supplementationNative pathwaysHuman cell culturesMolecular mechanismsSecondary metabolitesHuman cellsColibactinEfficient DNA interstrandObserved modulesPhenotype
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
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