2025
Spermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes
Singh P, Choi J, Cornillot E, Mamoun C. Spermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes. Science Advances 2025, 11: eadv2397. PMID: 40531988, PMCID: PMC12175890, DOI: 10.1126/sciadv.adv2397.Peer-Reviewed Original ResearchConceptsSpermidine biosynthesisIntracellular parasitesRegulate protein translationOxidative stress defenseDe novo synthesisProduction of reactive oxygen speciesTranslational regulationIncreased production of reactive oxygen speciesMolecular functionsProtein translationStress defensePlasmodium falciparum</i>Evolutionary adaptationReactive oxygen speciesAgent of human babesiosisIntraerythrocytic developmentBiosynthesisOxygen speciesHost erythrocytesTherapeutic targetStructural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin
Kim M, Kim J, Lee G, Olinares P, Airan Y, Chow J, Park J, Jeong Y, Park J, Chait B, Herzon S, Kim C, Kang J. Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin. Structure 2025 PMID: 40381618, DOI: 10.1016/j.str.2025.04.017.Peer-Reviewed Original ResearchNRPS-PKSCarrier proteinCryo-EM structurePKS enzymesPolyketide synthaseBiosynthesis mechanismBiosynthetic enzymesUpstream enzymesDimer interfaceColibactinBinding sitesDocking interactionsKetosynthasePromote colorectal cancerEnzymeStructural studiesGenomeBiosynthesisStructural detailsStructural analysisProteinGenotoxinsSynthaseHostCLBIBeyond Collagen Biosynthesis: Prolyl-3-Hydroxylase 1 Controls Extracellular Matrix Dynamics by Suppressing Transforming Growth Factor β2
Kandhari K, Merl-Pham J, Blumhagen R, Binzenhöfer L, Pijadina K, Stremlau M, Hennen E, Cabeza-Boeddinghaus N, Behr J, Hilgendorff A, Schwartz D, Yang I, Kaminski N, Hauck S, Eickelberg O, Staab-Weijnitz C. Beyond Collagen Biosynthesis: Prolyl-3-Hydroxylase 1 Controls Extracellular Matrix Dynamics by Suppressing Transforming Growth Factor β2. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a7635-a7635. DOI: 10.1164/ajrccm.2025.211.abstracts.a7635.Peer-Reviewed Original ResearchAn affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology
Seminara A, Hatzios S. An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology. Cell Chemical Biology 2025, 32: 486-497.e7. PMID: 40068683, PMCID: PMC12057763, DOI: 10.1016/j.chembiol.2025.02.004.Peer-Reviewed Original ResearchConceptsGastric pathogen Helicobacter pyloriHost-associated microbesOuter membrane transportersWild-type H. pyloriTransporter-deficient strainsPathogen Helicobacter pyloriNutrient-rich mediumBacterial physiologyMicrobial physiologyErgothioneine biosynthesisBacterial speciesMicrobial strainsComplex mediaCulture H. pyloriErgothioneineStrainHelicobacter pyloriPhysiologyH. pyloriComplicating effortsBiosynthesisTranscriptionFungalMicrobesHuman dietSuppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disordersHeme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis
Nair R, Vu A, Freer A, Bhatia K, Wang D, Savani M, Matulis S, Lonial S, Jaye D, Boise L, Seo S, Corson T, Nooka A, Bhatt S, McBrayer S, Gupta V, Hu X, Barwick B, Reddi A, Shanmugam M. Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis. Blood 2025, 145: 732-747. PMID: 39693611, PMCID: PMC12060166, DOI: 10.1182/blood.2024025690.Peer-Reviewed Original ResearchConceptsElectron transport chainBcl-2Heme biosynthesisBCL-2 antagonismElectron transport chain activityIron-containing prosthetic groupMultiple myelomaB-cell lymphoma 2MEK-ERK signalingGene signatureActivation of prosurvivalApoptotic thresholdPurine biosynthesisPenultimate enzymePyrimidine biosynthesisMetabolic rewiringTransport chainProtein kinaseMultiple Myeloma Research Foundation CoMMpass studyBiosynthesisPurine synthesisGenetic profilePrimary MM cellsProsthetic groupProgression-free survivalThioesters Support Efficient Protein Biosynthesis by the Ribosome
Kent A, Robins J, Knudson I, Vance J, Solivan A, Hamlish N, Fitzgerald K, Schepartz A, Miller S, Cate J. Thioesters Support Efficient Protein Biosynthesis by the Ribosome. ACS Central Science 2025, 11: 404-412. PMID: 40161951, PMCID: PMC11950863, DOI: 10.1021/acscentsci.4c01698.Peer-Reviewed Original ResearchProtein biosynthesisIn vitro translation reactionsCCA-adding enzymeEfficient protein biosynthesisAminoacyl-tRNA synthetasesTranslation machineryTranslation reactionsThioester intermediateRibosomeBiochemical reactionsEffective substrateThioesterBiosynthesisA-amino acidsTruncated tRNAsTRNATRNAsPeptide synthesisPolymer synthesisOxo-esterPrebiotic peptide synthesisSynthetaseXyloseExchange reactionFlexizymestRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells
Miao S, Li H, Song X, Liu Y, Wang G, Kan C, Ye Y, Liu R, Li H. tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells. Journal Of Experimental Medicine 2025, 222: e20240559. PMID: 39873720, PMCID: PMC11774205, DOI: 10.1084/jem.20240559.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsTumor-killing functionTransfer RNARegulating cholesterol biosynthesisAntitumor immunityCapacity of CD8+ T cellsActivation of CD8+ T cellsCholesterol biosynthesisM1A modificationTumor-killing capacityAntitumor responseATP citrate lyaseCancer immunotherapyCD8Effector functionsMetabolic reprogrammingProtein translationBiosynthetic demandsCitrate lyaseIn vitro assaysIn vivoPosttranscriptional mechanismsRegulatory checkpointsBiosynthesis
2024
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Hamchand R, Wang K, Song D, Palm N, Crawford J. Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca. Nature Communications 2024, 15: 8902. PMID: 39406708, PMCID: PMC11480411, DOI: 10.1038/s41467-024-53185-6.Peer-Reviewed Original ResearchConceptsK. oxytocaGeneral carbohydrate metabolismVirulence factor productionPLP-dependent enzymesAssociated with gutEnterobactin biosynthesisAutoinducer signalBacterial virulenceKlebsiella oxytocaSpecific carbohydratesHost immune responseCarbohydrate metabolismAutoinducerMolecular signalsVirulenceHistamine receptor H4BiosynthesisHost signalAcquisition responsesProtease inhibitorsPathwayHostLung pathologyLung isolationImmune response
2023
Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis
Attardo G, Benoit J, Michalkova V, Kondragunta A, Baumann A, Weiss B, Malacrida A, Scolari F, Aksoy S. Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis. IScience 2023, 26: 107108. PMID: 37534171, PMCID: PMC10391724, DOI: 10.1016/j.isci.2023.107108.Peer-Reviewed Original ResearchKennedy pathwayObligate endosymbiotic bacteriaViviparous tsetse flyLipid metabolismEarly developmental stagesInsect reproductionEndosymbiotic bacteriaSymbiotic bacteriaLipid biosynthesisPathway homeostasisSymbiont eliminationFunctional validationExperimental removalPhosphatidylcholine biosynthesisDevelopmental stagesProper functionTsetse fliesBiosynthesisLipid metabolism dysfunctionImpaired lipid metabolismMetabolismBacteriaPathwayMetabolism dysfunctionSymbiontsBiallelic mutations in LSS in autosomal‐recessive mutilating palmoplantar keratoderma
Zhou S, Jiang X, Zhu Y, Yang J, Yuan C, Chen M, Zhou Q, Lin Z, Li M. Biallelic mutations in LSS in autosomal‐recessive mutilating palmoplantar keratoderma. Experimental Dermatology 2023, 32: 699-706. PMID: 36811447, DOI: 10.1111/exd.14774.Peer-Reviewed Original ResearchConceptsLanosterol synthaseBiallelic mutationsLanosterol synthase genesPalmoplantar keratodermaPartial enzymatic activityHeterogeneous genetic diseaseExpression levelsMutilating palmoplantar keratodermaPathway of cholesterolBiosynthesis pathwayReduced expression levelsBiallelic variantsWild typeEnzymatic activityGenetic diseasesAutosomal-recessiveGenetic counselingMutationsMolecular characteristicsThin layer chromatographyLayer chromatographyMutantsBiosynthesisMale patientsChinese patientsGOT1 regulates CD8+ effector and memory T cell generation
Xu W, Patel C, Zhao L, Sun I, Oh M, Sun I, Helms R, Wen J, Powell J. GOT1 regulates CD8+ effector and memory T cell generation. Cell Reports 2023, 42: 111987. PMID: 36640309, PMCID: PMC9943022, DOI: 10.1016/j.celrep.2022.111987.Peer-Reviewed Original ResearchConceptsIntracellular redox balancePosttranslational regulationHIF proteinsMetabolic reprogrammingRedox balanceΑ-ketoglutarateGOT1T cell activationCell generationGenetic deletionEffector differentiationCritical roleCell activationDifferentiationRegulationProliferationReprogrammingBiosynthesisEffectorsProteinDeletionMechanisticallyCytotoxic functionFunctionPurineBump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells
Calle B, Gonzalez-Rodriguez E, Mahoney K, Cioce A, Bineva-Todd G, Tastan O, Roustan C, Flynn H, Malaker S, Schumann B. Bump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells. STAR Protocols 2023, 4: 101974. PMID: 36633947, PMCID: PMC9843269, DOI: 10.1016/j.xpro.2022.101974.Peer-Reviewed Original ResearchConceptsProtein substratesGlycosylation sitesGalNAc-T familyTransfection of cellsIndividual glycosyltransferasesBioorthogonal reportersN-acetylgalactosamine transferaseSubstrate specificityBiological functionsGalNAc-TsDisease relevanceMolecular biologyComplete detailsGlycosyltransferasesTransferaseCellsBiosynthesisBiologyReporterTransfectionGlycansSubstrateEnzymeHole engineeringSites
2022
High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development
Gihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development. Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.Peer-Reviewed Original ResearchConceptsCrystal structureHigh-throughput chemical screenHigh-resolution crystal structuresAntifungal drug developmentHigh-affinity inhibitorsEukaryotic pathogensChemical screenNew compoundsSingle chemotypeFunctional analysisLigand bindingAntifungal developmentPantothenate phosphorylationFungal isolatesPantothenate kinaseNew targetsFungiPanKPromising targetEnzymeDrug developmentNew mechanismCatalysisBiosynthesisKinaseKARRIKIN UP-REGULATED F-BOX 1 (KUF1) imposes negative feedback regulation of karrikin and KAI2 ligand metabolism in Arabidopsis thaliana
Sepulveda C, Guzmán MA, Li Q, Villaécija-Aguilar JA, Martinez SE, Kamran M, Khosla A, Liu W, Gendron JM, Gutjahr C, Waters MT, Nelson DC. KARRIKIN UP-REGULATED F-BOX 1 (KUF1) imposes negative feedback regulation of karrikin and KAI2 ligand metabolism in Arabidopsis thaliana. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2112820119. PMID: 35254909, PMCID: PMC8931227, DOI: 10.1073/pnas.2112820119.Peer-Reviewed Original ResearchConceptsKAI2-ligandsF-BOX 1Fire-prone environmentsArabidopsis thalianaNegative feedback loopKarrikinsNegative feedback regulationFeedback regulationExpression increasesPlantsGerminationLigand metabolismFeedback loopFurther activationMetabolismThalianaBiosynthesisGenesSpeciesRegulationPathwayActivationDiscoveryResponseGrowthRedesigning therapies for pantothenate kinase–associated neurodegeneration
Munshi MI, Yao SJ, Mamoun C. Redesigning therapies for pantothenate kinase–associated neurodegeneration. Journal Of Biological Chemistry 2022, 298: 101577. PMID: 35041826, PMCID: PMC8861153, DOI: 10.1016/j.jbc.2022.101577.Peer-Reviewed Original ResearchConceptsPantothenate kinase-associated neurodegenerationCellular metabolic processesMore common diseasesMetabolic processesPhysiological importancePANK2 genePantothenate kinaseCoenzyme ACoenzyme A.Rare genetic disorderCommon neurodegenerative diseaseNeurodegenerative diseasesGenetic disordersNeurodegenerationNew avenuesBiosynthesisKinaseGenesNew lightFuture investigationsCofactorMutationsCommon diseaseEnzymeAlzheimer's disease
2021
MMAB promotes negative feedback control of cholesterol homeostasis
Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCell Line, TumorCholesterolCholesterol, LDLFeedback, PhysiologicalGene Expression ProfilingHeLa CellsHep G2 CellsHomeostasisHumansHydroxymethylglutaryl CoA ReductasesLiverMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticReceptors, LDLRNA InterferenceSterol Regulatory Element Binding Protein 2ConceptsCholesterol biosynthesisCholesterol homeostasisMouse hepatic cell lineIntegrative genomic strategyIntricate regulatory networkMaster transcriptional regulatorCellular cholesterol levelsHMGCR activityLDL-cholesterol uptakeCholesterol levelsHuman hepatic cellsSterol contentGenomic strategiesTranscriptional regulatorsRegulatory networksIntracellular cholesterol levelsGene expressionUnexpected roleHepatic cell linesBiosynthesisMMABIntracellular levelsCell linesHomeostasisExpression of SREBP2Coupling lipid synthesis with nuclear envelope remodeling
Barger SR, Penfield L, Bahmanyar S. Coupling lipid synthesis with nuclear envelope remodeling. Trends In Biochemical Sciences 2021, 47: 52-65. PMID: 34556392, PMCID: PMC9943564, DOI: 10.1016/j.tibs.2021.08.009.Peer-Reviewed Original ResearchConceptsNuclear envelopeEndoplasmic reticulumNuclear membraneNuclear envelope remodelingLipid-protein interactionsBiosynthesis of lipidsNE remodelingGenome protectionDynamic remodeling processesNE dynamicsLipid speciesCell growthBilayer lipidsLipid synthesisNew roleMembraneLipidsRecent evidenceRemodeling processGenomeRemodelingBiosynthesisProtective barrierSpeciesProteinCombinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival
Wrobel C, Yu J, Rodrigues P, Ludewig A, Curtis B, Cohen S, Fox B, O’Donnell M, Sternberg P, Schroeder F. Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival. Journal Of The American Chemical Society 2021, 143: 14676-14683. PMID: 34460264, PMCID: PMC8594405, DOI: 10.1021/jacs.1c05908.Peer-Reviewed Original ResearchConceptsStarvation conditionsCombinatorial assemblyPremier model systemRelated nematode speciesModel organismsStarvation survivalClose homologueGenome editingBiosynthetic roleNematode speciesBiological functionsComparative metabolomicsDeletion resultsAmino acidsFirst insightModel systemMetabolite libraryLipid metabolismAdult animalsAssemblyCRISPRBiosynthesisHomologuesDularOrganismsEscherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis
Kim CS, Turocy T, Moon G, Shine EE, Crawford JM. Escherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis. Organic Letters 2021, 23: 6895-6899. PMID: 34406772, PMCID: PMC10577019, DOI: 10.1021/acs.orglett.1c02461.Peer-Reviewed Original ResearchConceptsFatty acid biosynthesisAcid biosynthesisHybrid polyketide-nonribosomal peptideNuclear magnetic resonance spectroscopyΓ-lactam derivativesUnknown biological activityBiosynthetic logicMagnetic resonance spectroscopyCancer initiationColorectal cancer initiationStereochemical analysisΓ-lactamsColibactinResonance spectroscopyDiverse collectionBiosynthesisBiological activityAbundant metabolitesPathwayRelated metabolitesRelated structuresMetabolitesLociProteinSpectroscopy
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