Vitamin in the crosshairs : targeting pantothenate and coenzyme a biosynthesis for new antituberculosis agents

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dc.contributor.authorButman, Hailey S.en_ZA
dc.contributor.authorKotze, Timothy J.en_ZA
dc.contributor.authorDowd, Cynthia S.en_ZA
dc.contributor.authorStrauss, Ericken_ZA
dc.date.accessioned2021-05-25T14:12:44Z
dc.date.available2021-05-25T14:12:44Z
dc.date.issued2020
dc.descriptionCITATION: Butman, H. S., et al. 2020. Vitamin in the crosshairs : targeting pantothenate and coenzyme a biosynthesis for new antituberculosis agents. Frontiers in Cellular and Infection Microbiology, 10:605662, doi:10.3389/fcimb.2020.605662.
dc.descriptionThe original publication is available at https://www.frontiersin.org
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractENGLISH ABSTRACT: Despite decades of dedicated research, there remains a dire need for new drugs against tuberculosis (TB). Current therapies are generations old and problematic. Resistance to these existing therapies results in an ever-increasing burden of patients with disease that is difficult or impossible to treat. Novel chemical entities with new mechanisms of action are therefore earnestly required. The biosynthesis of coenzyme A (CoA) has long been known to be essential in Mycobacterium tuberculosis (Mtb), the causative agent of TB. The pathway has been genetically validated by seminal studies in vitro and in vivo. In Mtb, the CoA biosynthetic pathway is comprised of nine enzymes: four to synthesize pantothenate (Pan) from L-aspartate and α-ketoisovalerate; five to synthesize CoA from Pan and pantetheine (PantSH). This review gathers literature reports on the structure/mechanism, inhibitors, and vulnerability of each enzyme in the CoA pathway. In addition to traditional inhibition of a single enzyme, the CoA pathway offers an antimetabolite strategy as a promising alternative. In this review, we provide our assessment of what appear to be the best targets, and, thus, which CoA pathway enzymes present the best opportunities for antitubercular drug discovery moving forward.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fcimb.2020.605662/full
dc.description.versionPublisher's version
dc.format.extent33 pagesen_ZA
dc.identifier.citationButman, H. S., et al. 2020. Vitamin in the crosshairs : targeting pantothenate and coenzyme a biosynthesis for new antituberculosis agents. Frontiers in Cellular and Infection Microbiology, 10:605662, doi:10.3389/fcimb.2020.605662
dc.identifier.issn2235-2988 (online)
dc.identifier.otherdoi:10.3389/fcimb.2020.605662
dc.identifier.urihttp://hdl.handle.net/10019.1/110513
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectVitaminen_ZA
dc.subjectMycobacterium aviumen_ZA
dc.subjectAntitubercular agentsen_ZA
dc.subjectDrug resistanceen_ZA
dc.subjectBiosynthesisen_ZA
dc.titleVitamin in the crosshairs : targeting pantothenate and coenzyme a biosynthesis for new antituberculosis agentsen_ZA
dc.typeArticleen_ZA
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