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The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.
Pubmed ID: 31558748
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View all literature mentionsMMV, a not-for-profit public-private partnership, was established as a foundation in Switzerland in 1999. Our mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs. Our vision is a world in which these innovative medicines will cure and protect the vulnerable and under-served populations at risk of malaria, and help to ultimately eradicate this terrible disease. Sponsors/Donors: -Bill and Melinda Gates Foundation -CRIMALDDI -ExxonMobil -Irish Aid -National Institutes of Health -Netherlands Ministry of Foreign Affairs -Rockefeller Foundation (former donor) -Secretaria de Estado de Cooperacin Internacional (Spanish Agency for International Cooperation) -Swiss Agency for Development and Cooperation -UK Department for International Development -USAID -Wellcome Trust -World Bank -World Health Organization
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