2019
Synthesis and reactivity of precolibactin 886
Healy AR, Wernke KM, Kim CS, Lees NR, Crawford JM, Herzon SB. Synthesis and reactivity of precolibactin 886. Nature Chemistry 2019, 11: 890-898. PMID: 31548676, PMCID: PMC6761996, DOI: 10.1038/s41557-019-0338-2.Peer-Reviewed Original ResearchConceptsStructural assignmentNucleophilic cleavageΑ-ketoiminesSpontaneous cyclizationSynthetic pathwayΑ-dicarbonylsBasic conditionsHPLC purificationBiosynthetic routeBiosynthetic intermediatesBiosynthesis of metabolitesCleavage pathwayBiosynthetic productsGut commensal Escherichia coliClb gene clusterCleavageCyclizationPyridoneAdductsIntermediatesCompoundsDNA crosslinkingSynthesisCrosslinkingMajor biosynthetic route
2018
Characterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening
Xue M, Shine E, Wang W, Crawford JM, Herzon SB. Characterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening. Biochemistry 2018, 57: 6391-6394. PMID: 30365310, PMCID: PMC6997931, DOI: 10.1021/acs.biochem.8b01023.Peer-Reviewed Original ResearchConceptsGenotoxic secondary metabolitesMethionine auxotrophic strainsE. coliGut commensal Escherichia coliClb gene clusterColibactin biosynthesisElectrophilic CyclopropanesGene clusterDNA alkylationPrevious biosynthetic studiesSecondary metabolitesAuxotrophic strainsEscherichia coliCommensal Escherichia coliBiosynthetic studiesFirst identificationBiosynthesisColiColibactinPUC19 DNAIsotopic labelingNucleotidesDNATandem mass spectrometryCertain strains
2016
A Mechanistic Model for Colibactin-Induced Genotoxicity
Healy AR, Nikolayevskiy H, Patel JR, Crawford JM, Herzon SB. A Mechanistic Model for Colibactin-Induced Genotoxicity. Journal Of The American Chemical Society 2016, 138: 15563-15570. PMID: 27934011, PMCID: PMC5359767, DOI: 10.1021/jacs.6b10354.Peer-Reviewed Original ResearchConceptsGene clusterE. coliDNA double-strand breaksDouble-strand breaksProbiotic Nissle 1917Clb gene clusterEukaryotic cellsCertain commensalDNA bindingProbiotic E. coliDisparate phenotypesPrecolibactinsAlkylate DNAColibactinIsolation effortsFermentation productsColiDNA alkylationDNANissle 1917Mechanistic modelSide chainsNatural productsMetabolite structuresEfficient DNA alkylation