2020
Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli
Park HB, Wei Z, Oh J, Xu H, Kim CS, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford JM. Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli. Nature Microbiology 2020, 5: 1319-1329. PMID: 32719505, PMCID: PMC7581551, DOI: 10.1038/s41564-020-0763-4.Peer-Reviewed Original ResearchConceptsAnti-inflammatory interleukin-10Colitis mouse modelInflammatory bowel diseaseColitis symptomsBowel diseaseInterleukin-10Immunological markersPathogenic roleImmunomodulatory metabolitesImmunomodulatory phenotypeGastrointestinal tractMouse modelImmunological activityPrimary human tissuesDrug stressSubinhibitory levelsHuman tissuesEnvironmental isolatesCertain strainsMetabolic pathwaysMetabolitesPatientsEscherichia coliSymptomsIBD
2010
Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures
Ehrlich KC, Chang P, Scharfenstein LL, Cary JW, Crawford JM, Townsend CA. Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures. FEMS Microbiology Letters 2010, 305: 65-70. PMID: 20158523, PMCID: PMC2891446, DOI: 10.1111/j.1574-6968.2010.01914.x.Peer-Reviewed Original ResearchConceptsBiosynthetic gene clusterAflatoxin biosynthesis genesCytochrome P450 monooxygenaseAflatoxin biosynthetic gene clusterWild-type A. flavusBiosynthesis genesGene clusterP450 monooxygenaseAflatoxin biosynthesisCarcinogenic aflatoxinsAccumulation of aflatoxinBiosynthesisA. flavusMinor toxinsO-methylsterigmatocystinAspergillus speciesFinal stepAspergillus flavusNew metabolitesQuantities of aflatoxinElevated quantitiesMutantsAccumulationFlavusGenes
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