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 patternsPolyketidesStructure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis
Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC. Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6246-6251. PMID: 20332208, PMCID: PMC2851968, DOI: 10.1073/pnas.0913531107.Peer-Reviewed Original ResearchConceptsPolyketide synthasesCrystal structureC bond formationPolyketide natural productsProduct release mechanismRing closure reactionAlpha/beta hydrolase foldSynthetic versatilitySynthetic potentialSubstrate-binding chamberIterative polyketide synthasesC cyclizationFatty acid synthasesBond formationClaisen cyclizationFirst mechanistic insightsProtein conformational changesNatural productsClosure reactionSubstrate positioningSide chainsBiosynthesis of aflatoxinSubstrate side chainDiverse architecturesPolyketide synthase A
2008
Deconstruction of Iterative Multidomain Polyketide Synthase Function
Crawford J, Thomas P, Scheerer J, Vagstad A, Kelleher N, Townsend C. Deconstruction of Iterative Multidomain Polyketide Synthase Function. Science 2008, 320: 243-246. PMID: 18403714, PMCID: PMC2480491, DOI: 10.1126/science.1154711.Peer-Reviewed Original ResearchConceptsIterative polyketide synthasesIndividual catalytic domainsProduct template (PT) domainsPolyketide synthasesStarter unitCatalytic domainAromatic polyketidesBiosynthetic enzymesTemplate domainSynthase functionCarcinogen aflatoxin B1PksAMechanistic featuresEnzymePt domainsKetosynthaseDomainPolyketidesBiosynthesisSynthasesCascadeReconstitutionAccumulationFamily