Enoyl-acyl carrier protein reductase (FabI) (FabI)

Plasmodium FabI, formally known as enoyl-acyl carrier protein reductase, is a critical enzyme in the Type II fatty acid synthesis (FAS II) pathway of the malaria parasite, particularly Plasmodium falciparum (UniProt Q965D5). This pathway is sequestered within the apicoplast, a unique relict plastid organelle essential for the parasite's survival and development (PMC1904404). FabI catalyzes the final, rate-limiting step of the fatty acid elongation cycle, utilizing NADH or NADPH to reduce trans-2-enoyl-ACP to acyl-ACP (Biochem J 2004, 381:719-724). Because humans utilize a distinct Type I FAS system, FabI is considered a highly selective therapeutic target with a low risk of off-target effects on host metabolism (PubMed 25105274). While its role in the symptomatic asexual blood stage has been a subject of debate, it is established as essential for the parasite's development during the liver stage, making it a prime candidate for prophylactic drug development (PMC1904404). Inhibitors such as the antimicrobial triclosan and various experimental flavonoids have been shown to potently inhibit the enzyme by forming stable ternary complexes, effectively halting the production of fatty acids necessary for organelle biogenesis (J Med Chem 2006, 49:3345-3353). Consequently, targeting Plasmodium FabI offers a promising strategy for both preventing infection and eradicating the parasite during its initial stages of host colonization (J Med Chem 2012, 55:10322-10344).

Other names

PfFabIEnoyl-ACP reductasetrans-2-enoyl-ACP reductasePfENREnoyl-[acyl-carrier-protein] reductase [NADH]

Inhibition of enoyl-acyl carrier protein reductase (FabI), which prevents the reduction of trans-2-enoyl-ACP to acyl-ACP, thereby blocking the Type II fatty acid synthesis (FAS II) pathway in the apicoplast (Biochem J 2004, 381:719-724).