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 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
2015
Lumiquinone A, an α‑Aminomalonate-Derived Aminobenzoquinone from Photorhabdus luminescens
Park HB, Crawford JM. Lumiquinone A, an α‑Aminomalonate-Derived Aminobenzoquinone from Photorhabdus luminescens. Journal Of Natural Products 2015, 78: 1437-1441. PMID: 25988621, PMCID: PMC5055755, DOI: 10.1021/np500974f.Peer-Reviewed Original Research
2013
Combinatorial Domain Swaps Provide Insights into the Rules of Fungal Polyketide Synthase Programming and the Rational Synthesis of Non‐Native Aromatic Products
Vagstad AL, Newman AG, Storm PA, Belecki K, Crawford JM, Townsend CA. Combinatorial Domain Swaps Provide Insights into the Rules of Fungal Polyketide Synthase Programming and the Rational Synthesis of Non‐Native Aromatic Products. Angewandte Chemie International Edition 2013, 52: 1718-1721. PMID: 23283670, PMCID: PMC3810244, DOI: 10.1002/anie.201208550.Peer-Reviewed Original Research
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
2009
Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization
Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 2009, 461: 1139-1143. PMID: 19847268, PMCID: PMC2872118, DOI: 10.1038/nature08475.Peer-Reviewed Original ResearchConceptsProduct templateX-ray crystal structurePt domainsIntramolecular aldol cyclizationCo-crystal structureIterative polyketide synthaseBicyclic compoundsPolyketide cyclizationNatural productsCrystal structureAldol cyclizationDiverse structuresBiological activityBiosynthetic reactionsCyclizationPolyketide synthaseAflatoxin B1Structural basisStructureIntermediatesCompoundsReactionPotent hepatocarcinogen aflatoxin B1TemplateHepatocarcinogen aflatoxin B1Production of Octaketide Polyenes by the Calicheamicin Polyketide Synthase CalE8: Implications for the Biosynthesis of Enediyne Core Structures
Belecki K, Crawford JM, Townsend CA. Production of Octaketide Polyenes by the Calicheamicin Polyketide Synthase CalE8: Implications for the Biosynthesis of Enediyne Core Structures. Journal Of The American Chemical Society 2009, 131: 12564-12566. PMID: 19689130, PMCID: PMC2760317, DOI: 10.1021/ja904391r.Peer-Reviewed Original Research
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 domainsKetosynthaseDomainPolyketidesBiosynthesisSynthasesCascadeReconstitutionAccumulationFamilySynthetic Strategy of Nonreducing Iterative Polyketide Synthases and the Origin of the Classical “Starter‐Unit Effect”
Crawford JM, Vagstad AL, Whitworth KP, Ehrlich KC, Townsend CA. Synthetic Strategy of Nonreducing Iterative Polyketide Synthases and the Origin of the Classical “Starter‐Unit Effect”. ChemBioChem 2008, 9: 1019-1023. PMID: 18338425, PMCID: PMC3182100, DOI: 10.1002/cbic.200700702.Peer-Reviewed Original ResearchStarter unit specificity directs genome mining of polyketide synthase pathways in fungi
Crawford JM, Vagstad AL, Ehrlich KC, Townsend CA. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi. Bioorganic Chemistry 2008, 36: 16-22. PMID: 18215412, PMCID: PMC3200548, DOI: 10.1016/j.bioorg.2007.11.002.Peer-Reviewed Original ResearchConceptsHybrid metabolitesPathogenic fungus Coccidioides immitisPolyketide synthase pathwayHuman fungal pathogenSAT domainAflatoxin clusterGenome miningSynthase subunitsPolyketide synthasePKS clustersACP domainStarter unitProtein databasePolyketide synthesisFungal pathogensFunctional similarityHexanoyl-CoA.Fatty acid productsEscherichia coliSynthase pathwayFungiFungus Coccidioides immitisAspergillus speciesPathwayDomain
2006
Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase
Crawford JM, Dancy BC, Hill EA, Udwary DW, Townsend CA. Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 16728-16733. PMID: 17071746, PMCID: PMC1636523, DOI: 10.1073/pnas.0604112103.Peer-Reviewed Original Research