Coenzyme A Biosynthesis Targeting in Malaria Parasites
Summary
Malaria remains a major global health burden, driven by the complex life cycle of Plasmodium parasites within human and mosquito hosts. A critical vulnerability is the parasite’s inability to synthesise pantothenate (vitamin B5), which it must import from its environment to assemble coenzyme A (CoA). The conversion of pantothenate to CoA occurs via a conserved five-step enzymatic cascade, beginning with pantothenate kinase and culminating in the generation of the active thiol cofactor. CoA is indispensable for fatty acid metabolism, histone acetylation and other acyl-transfer reactions that underpin parasite growth and transmission. Strategies to disrupt this pathway include designing substrate analogues that inhibit key enzymes, allosteric regulators of pantothenate uptake and mosquito-targeted interventions to deprive the parasite of essential nutrients. By obstructing CoA biosynthesis, these approaches aim both to arrest blood-stage replication in humans and to block parasite development in the mosquito vector.
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Coenzyme A Biosynthesis Targeting in Malaria Parasites publication trend
The graph below shows the total number of articles in coenzyme a biosynthesis targeting in malaria parasites across all publications each year (not limited to Nature Index journals).
Technical terms
Pantothenate: A water-soluble vitamin B5 that serves as the essential precursor for CoA synthesis in malaria parasites.
Pantothenate kinase (PanK): The first and rate-limiting enzyme in the CoA biosynthetic cascade, phosphorylating pantothenate to 4′-phosphopantothenate.
Pantothenamides: Synthetic analogues of pantothenate that inhibit CoA biosynthesis or CoA-utilising enzymes by acting as substrate mimics.
Coenzyme A (CoA): A pivotal cofactor in acyl-group transfer reactions, essential for fatty acid metabolism and energy production in the parasite.
References
- Starving the Beast: Limiting Coenzyme A Biosynthesis to Prevent Disease and Transmission in Malaria. International Journal of Molecular Sciences (2023).
- Characterization of the Sodium Multi-Vitamin Transporter in the Mosquito Anopheles stephensi and Its Capacity to Mobilize Pantothenate and Biotin. Biomolecules (2025).
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets. PLOS Pathogens (2021).
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