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
2016
Convergent and Modular Synthesis of Candidate Precolibactins. Structural Revision of Precolibactin A
Healy AR, Vizcaino MI, Crawford JM, Herzon SB. Convergent and Modular Synthesis of Candidate Precolibactins. Structural Revision of Precolibactin A. Journal Of The American Chemical Society 2016, 138: 5426-5432. PMID: 27025153, PMCID: PMC5049697, DOI: 10.1021/jacs.6b02276.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
Not just passing through
Crawford JM, Clardy J. Not just passing through. Nature Chemistry 2010, 2: 805-807. PMID: 20861892, DOI: 10.1038/nchem.848.Peer-Reviewed Original ResearchStructure 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 B1
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