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Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor

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posted on 24.11.2021, 20:19 by AL Valenciano, ML Fernández-Murga, EF Merino, NR Holderman, GJ Butschek, Karl ShafferKarl Shaffer, Peter TylerPeter Tyler, MB Cassera
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.

History

Preferred citation

Valenciano, A. L., Fernández-Murga, M. L., Merino, E. F., Holderman, N. R., Butschek, G. J., Shaffer, K. J., Tyler, P. C. & Cassera, M. B. (2019). Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor. Scientific Reports, 9(1), 13936-. https://doi.org/10.1038/s41598-019-50319-5

Journal title

Scientific Reports

Volume

9

Issue

1

Publication date

01/12/2019

Pagination

13936

Publisher

Springer Science and Business Media LLC

Publication status

Published

Online publication date

26/09/2019

ISSN

2045-2322

eISSN

2045-2322

Article number

13936

Language

en