Plasmodium falciparum acyl-CoA synthetase 10 (PfACS10)

Plasmodium falciparum acyl-CoA synthetase 10 (PfACS10) is an essential enzyme involved in the lipid metabolism of the malaria parasite. It belongs to a family of enzymes that catalyze the activation of fatty acids by converting them into acyl-CoA thioesters, a critical step for the synthesis of triacylglycerols and other complex lipids. PfACS10 is particularly vital during the asexual blood stage of the parasite's life cycle, where it supports rapid membrane biogenesis and energy storage. Inhibition of PfACS10 by small molecules, such as those identified in the Medicines for Malaria Venture (MMV) library, leads to a significant reduction in triacylglycerol production and the accumulation of fatty acid precursors, ultimately resulting in parasite death. Mutations in the PfACS10 gene, such as M300I and A268D, have been identified as mechanisms of resistance to these inhibitors, highlighting its role as a chemically validated drug target.

Other names

PfACS10PF3D7_0525100Acyl-CoA synthetase 10Long-chain-fatty-acid--CoA ligase 10

Inhibition of PfACS10 disrupts the activation of fatty acids into acyl-CoA thioesters, leading to a reduction in triacylglycerol levels and an accumulation of lipid precursors, which impairs parasite membrane integrity and survival.