Adipostatins E-J, new potent antimicrobials identified as inhibitors of coenzyme-A biosynthesis

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dc.creatorGómez Rodríguez, Lyanne
dc.creatorSchultz, Pamela J.
dc.creatorTamayo Castillo, Giselle
dc.creatorDotson, Garry D.
dc.creatorSherman, David H.
dc.creatorTripathi, Ashootosh
dc.date.accessioned2021-01-26T19:54:47Z
dc.date.available2021-01-26T19:54:47Z
dc.date.issued2020-01
dc.date.updated2021-01-25T20:17:04Z
dc.description.abstractPhosphopantetheine is a key structural element in biological acyl transfer reactions found embedded within coenzyme A (CoA). Phosphopantothenoylcysteine synthetase (PPCS) is responsible for installing a cysteamine group within phosphopantetheine. Therefore, it holds considerable potential as a drug target for developing new antimicrobials. In this study, we adapted a biochemical assay specific for bacterial PPCS to screen for inhibitors of CoA biosynthesis against a library of marine microbial derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces blancoensis led to the isolation of novel antibiotics (10-12, and 14) from the adipostatin class of molecules. The most potent molecule (10) displayed in vitro activity with IC50 = 0.93 µM, against S. pneumoniae PPCS. The whole cell antimicrobial assay against isolated molecules demonstrated their ability to penetrate bacterial cells and inhibit clinically relevant pathogenic strains. This establishes the validity of PPCS as a pertinent drug target, and the value of NPEs to provide new antibiotics.es_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA)es_ES
dc.description.procedenceUCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Químicaes_ES
dc.description.sponsorshipInternational Cooperative Biodiversity Groups/[U01 TW007404]/ICBG/Estados Unidoses_ES
dc.description.sponsorshipHans W. Vahlteich Professorship/[NIH R35 GM118101]//Estados Unidoses_ES
dc.description.sponsorshipUniversity of Michigan/[5T32GM008597]//Estados Unidoses_ES
dc.description.sponsorshipRackham Merit Fellowship/[]/RMF/Estados Unidoses_ES
dc.identifier.citationhttps://www.sciencedirect.com/science/article/abs/pii/S0040403919312687?via%3Dihub#!
dc.identifier.doi10.1016/j.tetlet.2019.151469
dc.identifier.issn0040-4039
dc.identifier.urihttps://hdl.handle.net/10669/82612
dc.language.isoen_USes_ES
dc.relation.ispartof
dc.rightsacceso embargado
dc.sourceTetrahedron Letters 61(5), pp.1-6es_ES
dc.subjectNatural productses_ES
dc.subjectAntibioticses_ES
dc.subjectCoenzyme A biosynthesises_ES
dc.subjectPhosphopantothenoylcysteine synthetasees_ES
dc.titleAdipostatins E-J, new potent antimicrobials identified as inhibitors of coenzyme-A biosynthesises_ES
dc.typeartículo original

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