2021
Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies
Wernke KM, Tirla A, Xue M, Surovtseva YV, Menges FS, Herzon SB. Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies. Journal Of The American Chemical Society 2021, 143: 15824-15833. PMID: 34524796, DOI: 10.1021/jacs.1c07559.Peer-Reviewed Original ResearchConceptsFanconi anemia DNA repair pathwayBiosynthetic gene clusterDNA repair pathwaysGene clusterRepair pathwaysDNA bindingBacterial phenotypesInduces DNAGenotoxic effectsHuman microbiomeColibactinBiosynthetic precursorNatural product structuresBiological studiesPathwayStructure-activity relationshipsAction studiesGenotoxic metabolitesOrganismsOncogenesisDNATumorigenesisMicrobiomeFacilitate mechanismsPhenotype
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 ResearchMeSH KeywordsAlkylationCell Line, TumorCross-Linking ReagentsDNADNA Breaks, Double-StrandedEscherichia coliHumansMutagensPeptidesPolyketidesConceptsHost 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