2024
The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching
Lam Y, Hamchand R, Mucci N, Kauffman S, Dudkina N, Reagle E, Casanova-Torres Á, DeCuyper J, Chen H, Song D, Thomas M, Palm N, Goodrich-Blair H, Crawford J. The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching. Applied And Environmental Microbiology 2024, 90: e00528-24. PMID: 38916293, PMCID: PMC11267870, DOI: 10.1128/aem.00528-24.Peer-Reviewed Original ResearchRegulatory hierarchyG protein-coupled receptorsSmall molecule signalsHost-bacteria interactionsSymbiotic relationshipNatural productsHuman G protein-coupled receptorsAmino acid metabolismRegulating amino acid metabolismNull mutantsDiverse natural productsSecondary metabolismNematode progeny productionPathogen interactionsGlobal regulatorNematode egg hatchingWild typeInsect hostsSecondary metabolitesHatching rateLrhAAcylated appendagesMolecular networksMolecule signalsAmide signals
2023
Editorial: Fungal secondary metabolites as valuable chemical entities for medicines and agrochemicals
Wang W, Wang T. Editorial: Fungal secondary metabolites as valuable chemical entities for medicines and agrochemicals. Frontiers In Microbiology 2023, 14: 1150023. PMID: 36814564, PMCID: PMC9939815, DOI: 10.3389/fmicb.2023.1150023.Peer-Reviewed Original ResearchFungal secondary metabolitesSecondary metabolites
2022
Front Cover: Guignardones Y–Z, Antiviral Meroterpenes from Penicillium sp. NBUF154 Associated with a Crella Sponge from the Marine Mesophotic Zone (Chem. Biodiversity 8/2022)
Zou J, Wu J, Ding L, Wang W, Liu Y, Feng Y, Lai Q, Lin W, Wang T, He S. Front Cover: Guignardones Y–Z, Antiviral Meroterpenes from Penicillium sp. NBUF154 Associated with a Crella Sponge from the Marine Mesophotic Zone (Chem. Biodiversity 8/2022). Chemistry & Biodiversity 2022, 19 DOI: 10.1002/cbdv.202200724.Peer-Reviewed Original ResearchCoral reef habitatsMesophotic coral ecosystemsCoral ecosystemsReef habitatsMesophotic zoneSponge-associated fungiActive secondary metabolitesShallow counterpartsPenicillium spFungus Penicillium spSecondary metabolitesSpGuignardone AFermentation brothEcosystemsHabitatsEC50 valuesMCESpongesBroad spectrumMeroterpenesBlumenol AFungiNew meroterpenesLast decadeSecondary Metabolism Gene Clusters Exhibit Increasingly Dynamic and Differential Expression during Asexual Growth, Conidiation, and Sexual Development in Neurospora crassa
Wang Z, Lopez-Giraldez F, Slot J, Yarden O, Trail F, Townsend JP. Secondary Metabolism Gene Clusters Exhibit Increasingly Dynamic and Differential Expression during Asexual Growth, Conidiation, and Sexual Development in Neurospora crassa. MSystems 2022, 7: e00232-22. PMID: 35638725, PMCID: PMC9239088, DOI: 10.1128/msystems.00232-22.Peer-Reviewed Original ResearchConceptsSM clustersComparative genomicsSecondary metabolitesAsexual growthN. crassaNeurospora crassaSecondary metabolism gene clustersSexual developmentDevelopmental stagesSecondary metabolite clustersComparative genomic analysisExtensive transcriptomic dataGene expression patternsEnvironmental conditionsFungal toxin productionLevel of RNASMC genesLife cycleRegulatory switchComputational annotationGene clusterEnvironmental signalsMetabolite clustersGenomic analysisKnockout phenotypes
2021
A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides
Li JH, Cho W, Hamchand R, Oh J, Crawford JM. A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides. Journal Of Natural Products 2021, 84: 2692-2699. PMID: 34581573, PMCID: PMC9970011, DOI: 10.1021/acs.jnatprod.1c00573.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetasePeptide synthetaseBiosynthetic gene clusterComparative genomic analysisFree-living infective juvenilesNRPS genesEffector proteinsInsect larvaeSpecialized metabolitesGene clusterMutualistic relationshipXenorhabdus bovieniiHeterologous expressionGenomic analysisRichest producersEntomopathogenic bacteriumSecondary metabolitesHost larvaeInfective juvenilesTermination domainInhibitor pathwayExogenous alcoholsLarvaeSpeciesComplex array
2020
Structure and bioactivity of colibactin
Wernke KM, Xue M, Tirla A, Kim CS, Crawford JM, Herzon SB. Structure and bioactivity of colibactin. Bioorganic & Medicinal Chemistry Letters 2020, 30: 127280. PMID: 32527463, PMCID: PMC7309967, DOI: 10.1016/j.bmcl.2020.127280.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaStrands of DNABiosynthetic pathwaySecondary metabolitesColibactinMolecular-level explanationHuman gutAdenine residuesCell contactElectrophilic CyclopropanesCertain strainsBacteriaGenotoxic effectsHeterodimersDNABacterial cultureResiduesPathwayCleavageCellsStrandsGutNeonatal comorbidities and gasotransmitters
Gentle S, Tipple T, Patel R. Neonatal comorbidities and gasotransmitters. Nitric Oxide 2020, 97: 27-32. PMID: 32014495, DOI: 10.1016/j.niox.2020.01.012.Peer-Reviewed Original ResearchConceptsRegulating various signaling pathwaysHypoxic ischemic encephalopathyFormation of secondary metabolitesTherapeutic attenuationNeonatal comorbiditiesNecrotizing enterocolitisPulmonary hypertensionIschemic encephalopathyNeonatal physiologyVasodilatory effectSecondary metabolitesSignaling pathwayGasotransmitter hydrogen sulfideConstitutive productionNitric oxideMolecule productionTherapeutic supplementAnti-microbialCellular deathInduce productionAnti-inflammatoryComorbiditiesEndogenous formationEnterocolitisMarine Sponge-Associated Fungi as Potential Novel Bioactive Natural Product Sources for Drug Discovery: A Review
Zhang B, Zhang T, Xu J, Lu J, Qiu P, Wang T, Ding L. Marine Sponge-Associated Fungi as Potential Novel Bioactive Natural Product Sources for Drug Discovery: A Review. Mini-Reviews In Medicinal Chemistry 2020, 20: 1966-2010. PMID: 32851959, DOI: 10.2174/1389557520666200826123248.Peer-Reviewed Original ResearchConceptsNatural productsNovel bioactive natural productsDrug discoveryNatural product sourcesBioactive natural productsBioactive secondary metabolitesMarine sponge-associated fungiSponge-associated fungiNew compoundsStructural diversityMarine fungiBiological functionsBiological activityProduct sourcesSecondary metabolitesDifferent structural classesFungiStructural classesCompoundsPromising sourceMeroterpenoidsMoleculesProductsPolyketidesDiscovery
2019
Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
Aung TN, Nourmohammadi S, Qu Z, Harata-Lee Y, Cui J, Shen HY, Yool AJ, Pukala T, Du H, Kortschak RD, Wei W, Adelson DL. Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle. Scientific Reports 2019, 9: 14200. PMID: 31578346, PMCID: PMC6775143, DOI: 10.1038/s41598-019-50271-4.Peer-Reviewed Original ResearchConceptsCompound Kushen InjectionExperimental biology approachesEffect of CKIPlant secondary metabolitesCytokine Signaling PathwaysCKI activityBiology approachReconstitution approachGene expressionCell cyclePhenotype dataSignaling pathwaysSecondary metabolitesBreast cancer cell linesCancer cell linesKushen InjectionSingle major compoundCell linesApoptosisLiquid chromatography fractionationCell viabilityHigh-performance liquid chromatography fractionationMajor compoundsComplex fashionCandidate mechanismStructure elucidation of colibactin and its DNA cross-links
Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, Shine EE, Wang W, Herzon SB, Crawford JM. Structure elucidation of colibactin and its DNA cross-links. Science 2019, 365 PMID: 31395743, PMCID: PMC6820679, DOI: 10.1126/science.aax2685.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaCell biology dataColibactin gene clusterCombination of geneticsComplex secondary metabolitesGene clusterIsotope labelingSecondary metabolitesBiology dataColibactinHuman gutTandem mass spectrometryBacteriaPhysiological effectsMass spectrometryStructure elucidationGutGeneticsDNAEnzymeChemical synthesisEscherichiaElucidationMetabolitesLabelingUnderstanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection With Transcriptome Analysis
Shen H, Qu Z, Harata-Lee Y, Aung TN, Cui J, Wang W, Kortschak RD, Adelson DL. Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection With Transcriptome Analysis. Frontiers In Oncology 2019, 9: 632. PMID: 31380274, PMCID: PMC6660286, DOI: 10.3389/fonc.2019.00632.Peer-Reviewed Original ResearchTranscriptome analysisCompound Kushen InjectionPlant secondary metabolitesSingle herb extractsTranscriptome dataHerbal compatibilityDNA replicationKushen InjectionImmune-related pathwaysMDA-MB-231 cellsGene expressionCell cycleIL-1β protein expressionSecondary metabolitesIL-1β gene expressionTraditional Chinese medicine formulationChinese medicine formulationMechanistic contributionsProtein expressionELISA assaysCytotoxic effectsHerbal medicinePathwayHerbal extractsMedicine formulation
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 ResearchConceptsHost 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 modulesPhenotypeCharacterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening
Xue M, Shine E, Wang W, Crawford JM, Herzon SB. Characterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening. Biochemistry 2018, 57: 6391-6394. PMID: 30365310, PMCID: PMC6997931, DOI: 10.1021/acs.biochem.8b01023.Peer-Reviewed Original ResearchConceptsGenotoxic secondary metabolitesMethionine auxotrophic strainsE. coliGut commensal Escherichia coliClb gene clusterColibactin biosynthesisElectrophilic CyclopropanesGene clusterDNA alkylationPrevious biosynthetic studiesSecondary metabolitesAuxotrophic strainsEscherichia coliCommensal Escherichia coliBiosynthetic studiesFirst identificationBiosynthesisColiColibactinPUC19 DNAIsotopic labelingNucleotidesDNATandem mass spectrometryCertain strains
2017
Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway
Guntaka NS, Healy AR, Crawford JM, Herzon SB, Bruner SD. Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway. ACS Chemical Biology 2017, 12: 2598-2608. PMID: 28846367, PMCID: PMC5830302, DOI: 10.1021/acschembio.7b00479.Peer-Reviewed Original ResearchConceptsColibactin gene clusterÅ crystal structurePolyketide secondary metabolitesAcyl-thioester substratesColibactin biosynthesisGene clusterBiosynthetic pathwayAtypical roleGene productsBiochemical characterizationFunctional analysisSecondary metabolitesGreater catalytic efficiencyCancer formationColorectal cancer formationHuman gutSpecific functionsNovel insightsCarrier proteinThioesteraseGenetic deletionClbQColibactinCatalytic efficiencyPathway
2016
Plant-Mediated Effects on Mosquito Capacity to Transmit Human Malaria
Hien D, Dabiré K, Roche B, Diabaté A, Yerbanga R, Cohuet A, Yameogo B, Gouagna L, Hopkins R, Ouedraogo G, Simard F, Ouedraogo J, Ignell R, Lefevre T. Plant-Mediated Effects on Mosquito Capacity to Transmit Human Malaria. PLOS Pathogens 2016, 12: e1005773. PMID: 27490374, PMCID: PMC4973987, DOI: 10.1371/journal.ppat.1005773.Peer-Reviewed Original ResearchConceptsImportant African malaria vectorsHost resource availabilityMalaria parasitesMalaria vectorsSugar sourcesSugar mealsAfrican malaria vectorsToxic secondary metabolitesNutritional ecologyPlant speciesMosquito traitsMosquito competenceNatural diversityFeeding assaysLannea microcarpaMosquito's capacityEcological contextSecondary metabolitesMolecular aspectsMalaria transmissionParasite growthResource availabilityDirect membrane feeding assaysDevelopment durationHuman malaria
2015
Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways
Engel P, Vizcaino MI, Crawford JM. Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways. Applied And Environmental Microbiology 2015, 81: 1502-1512. PMID: 25527542, PMCID: PMC4309719, DOI: 10.1128/aem.03283-14.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetaseBiosynthetic pathwayBacterial symbiontsGut symbiontsSecondary metabolitesEukaryotic cellsGenomic islandsBacterial gut symbiontDiverse symbiotic associationsDivergent variantsDNA damagePolyketide synthase pathwayE. coliComparative metabolomic analysisRelated secondary metabolitesPathway-dependent mannerSymbiotic associationGene clusterMicrobial interactionsBiosynthesis pathwayDistinct hostsPeptide synthetaseMammalian gutHoney beesSymbionts
2012
A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States
Somvanshi VS, Sloup RE, Crawford JM, Martin AR, Heidt AJ, Kim KS, Clardy J, Ciche TA. A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States. Science 2012, 337: 88-93. PMID: 22767929, PMCID: PMC4006969, DOI: 10.1126/science.1216641.Peer-Reviewed Original ResearchConceptsNematode intestinePromoter inversionVariable life historiesM-form cellsInsect infectionHost nematodesLife historyMicrobial populationsSecondary metabolitesAntibiotic toleranceIndividual cellsNematodesPhotorhabdusM formJuvenile offspringCellsPathogenic variantsFirst cellsDistinct formsMutualistsMutualismVariantsInsectsAvirulenceSmall cell variant
1990
Spatial and Temporal Expression of Regulatory Genes in Zea mays
Tonelli C, Consonni G, Mereghetti M, Dolfini S, Dellaporta S, Viotti A, Gavazzi G. Spatial and Temporal Expression of Regulatory Genes in Zea mays. Current Plant Science And Biotechnology In Agriculture 1990, 9: 385-390. DOI: 10.1007/978-94-009-2103-0_58.Peer-Reviewed Original ResearchRegulatory genesPigmentation of flowersDifferent regulatory genesPlant defenseFlavonoid biosynthesisGene regulationStructural geneDevelopmental biologyNumerous genesZea maysSecondary metabolitesDistribution of pigmentsGenesTemporal expressionEnvironmental stimuliNutrient supplySpecific functionsBiosynthesisModel systemCoordinate wayPlantsPigmentationPhytopathogensMaysFlowers
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