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Although apicoplast FASII is essential for\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    growth within mosquitoes and the human liver, this pathway is dispensable and largely inactive in blood-stage parasites that can scavenge host fatty acids. In contrast to FASII enzymes that can be disrupted without fitness defect, we report that knockout or ligand-dependent knockdown of apicoplast ACP is lethal to blood-stage\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , indicating an essential FASII-independent function. Loss of ACP impairs the biosynthesis of essential isoprenoid precursors and blocks apicoplast biogenesis. Using proximity biotinylation and biochemical interaction studies, we identified a key role for ACP in binding and stabilizing apicoplast pyruvate kinase II (PKII). This critical enzyme is the only known source of nucleoside triphosphates (NTPs) in this organelle and is required for isoprenoid synthesis and apicoplast biogenesis. Our work reveals that ACP knockdown results in destabilization and loss of PKII, which is sufficient to explain ACP essentiality in this stage. This work unveils essential ACP function at a key biochemical hub controlling broad apicoplast metabolism in malaria parasites that is independent of the canonical ACP role in FASII.\n                  <\/jats:p>","DOI":"10.7554\/elife.111494","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:30:18Z","timestamp":1782311418000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.111494","source":"Crossref","is-referenced-by-count":0,"title":["Acyl carrier protein is essential for apicoplast biogenesis in malaria parasites independent of fatty acid synthesis"],"prefix":"10.7554","volume":"15","author":[{"given":"Sage WR","family":"Geher","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03r0ha626","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Utah School of Medicine","place":["Salt Lake City, United 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