The carotenoid biosynthesis pathway in the asexual intraerythrocytic stages of Plasmodium falciparum

Nortey-Mensah R, Teye MA, Ofori MF. 2021. The carotenoid biosynthesis pathway in the asexual intraerythrocytic stages of Plasmodium falciparum. Asian J Trop Biotechnol 18: 13-27. Plasmodium falciparum, like other Apicomplexans, possesses a dormant plastid called the apicoplast. Because it houses metabolic pathways peculiar to the parasite, such as isoprenoid production, this organelle promises a new and promising target for the chemotherapeutic control of malaria. Although the phytoene synthase (PSY) gene has been shown to be critical for carotenogenesis, nothing is known about its evolutionary relationship with P. falciparum and other Apicomplexans. The goal of this work was to identify the evolutionary history and relatedness of the PSY gene in Apicomplexans and other animals, as well as to profile the carotenoids generated in the asexual intraerythrocytic stages of P. falciparum. Fluridone's IC50 and effect on parasite population were determined utilizing in vitro inhibition experiments on the asexual intraerythrocytic stages of P. falciparum. To examine the evolutionary history and relatedness of the PSY gene in Apicomplexans and other taxa, HPLC was used to profile carotenoids created at the asexual phases, and an unrooted phylogenetic tree was built using MEGA 6. Dose-dependent inhibition of parasite population was observed with fluridone treatment on all the asexual stages, with the ring stages being the most vulnerable. The carotenoid profiles revealed that carotenoids are generated cumulatively in P. falciparum throughout the asexual intraerythrocytic phases, with carotenoids such as lycopene, ?-, ?-carotene among those synthesized. The discovery of relatively high quantities of abscisic acid (ABA) in the schizont stages but not in the other stages was an interesting novel finding of this study. This is the first time ABA has been shown to be synthesized by P. falciparum, and additional research into the specific role of ABA in P. falciparum schizont phases would be groundbreaking. The phylogenetic study revealed that the P. falciparum PSY was most closely related to P. reichenowi, a chimpanzee strain of the malaria-causing parasites, supporting the hypothesis that malaria species in humans originated in chimps.