Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis
, 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.
Authors
- Megan Okada (ORCID: https://orcid.org/0000-0003-4398-9819)
- Sage W R Geher
- Russell Swift (ORCID: https://orcid.org/0000-0003-1442-9740)
- Seyi Falekun (ORCID: https://orcid.org/0000-0003-2280-4424)
- Sean T. Prigge (ORCID: https://orcid.org/0000-0001-9684-1733)
- Jessica Pita-Aquino (ORCID: https://orcid.org/0000-0002-4333-214X)
- Paul A. Sigala (ORCID: https://orcid.org/0000-0002-3464-3042)
- James A Wohlschlegel
- Yasaman Jami-Alahmadi
Institutions
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- University of Utah (US)
- Johns Hopkins Medicine (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-03-31
- DOI
- https://doi.org/10.64898/2026.03.29.713301
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Heart Association
- Johns Hopkins University
- Bloomberg Philanthropies
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases