Jagbir Singh, Rani Mansuri, Pravin Kumar Atul, Arun Sharma and Mahesh Kumar
The growing resistance to current antimalarial drugs is a major concern for global public health, demands the novel essential regulatory pathway of plasmodium to be targeted for new potent antimalarial development. The biological processes that regulate both growth and gametocytogenesis of plasmodium still remain unknown. Identification and thorough understanding of such pathways is crucial to the development of a new generation of dual activity antimalarials that can inhibit both infection and transmission. There one pathway responsible for phosphatidylcholine (PC) a phospholipid biosynthesis in Bacteria, eukaryotes and plants through different routes, has also been elucidated in plasmodium. Plasmodium normally synthesizes PC for membrane development from choline through CDP-choline route but at infection stage in host it needs faster development of PC abundantly for membrane development from serine of the host blood through plant like serine-decarboxylase-phosphoethanolamine-methyltransferase (SDPM) alternate pathway absent in human host. Phosphoethanolamine methyltransferase (PMT) an enzyme crucial for catalyzing trimethylation, a rate limiting step to synthesize PC is a promising target for research on a novel class of antimalarials. In this review, we have emphasized development of PC biosynthesis through SDPM pathway and the significance of PC in Plasmodium to provide novel directions in which research might be most beneficial. We also focused on important perspectives and applicability of PMTs as therapeutic target for structure-based drug designing for PMT inhibitor discovery as antimalarials.
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