A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or ''apicoplast,'' is indispensable, but the complete sequence of both the Plasmodium falciparum and Toxoplasma gondii apicoplast genomes has offered no clue as to what essential metabolic function(s) this organelle might perform in parasites. To investigate possible functions of the apicoplast, we sought to identify nuclear-encoded genes whose products are targeted to the apicoplast in Plasmodium and Toxoplasma. We describe here nuclear genes encoding ribosomal proteins S9 and L28 and the fatty acid biosynthetic enzymes acyl carrier protein (ACP), ␤-ketoacyl-ACP synthase III (FabH), and ␤-hydroxyacyl-ACP dehydratase (FabZ). These genes show high similarity to plastid homologues, and immunolocalization of S9 and ACP verifies that the proteins accumulate in the plastid. All the putatively apicoplast-targeted proteins bear N-terminal presequences consistent with plastid targeting, and the ACP presequence is shown to be sufficient to target a recombinant green f luorescent protein reporter to the apicoplast in transgenic T. gondii. Localization of ACP, and very probably FabH and FabZ, in the apicoplast implicates fatty acid biosynthesis as a likely function of the apicoplast. Moreover, inhibition of P. falciparum growth by thiolactomycin, an inhibitor of FabH, indicates a vital role for apicoplast fatty acid biosynthesis. Because the fatty acid biosynthesis genes identified here are of a plastid͞bacterial type, and distinct from those of the equivalent pathway in animals, fatty acid biosynthesis is potentially an excellent target for therapeutics directed against malaria, toxoplasmosis, and other apicomplexan-mediated diseases.

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▪ Abstract  Plasmodium falciparum is an obligate human parasite that is the causative agent of the most lethal form of human malaria. Transmission of P. falciparum to a new human host requires a mosquito vector within which sexual replication occurs. P. falciparum replicates as an intracellular parasite in man and as an extracellular parasite in the mosquito, and it undergoes multiple developmental changes in both hosts. Changes in the environment and the activities of parasites in these various life-cycle stages are likely to be reflected in changes in the metabolic needs and capabilities of the parasite. Most of our knowledge of the metabolic capabilities of P. falciparum is derived from studies of the asexual erythrocytic cycle of the parasite, the portion of the parasite life cycle found in infected humans that is responsible for malarial symptoms. Efforts to control transmission and to understand the sometimes unique biology of this parasite have led to information about the metabolic capabilities of sexual and/or sporogonic stages of these parasites. This review focuses on comparing and contrasting the carbohydrate, nucleic acid, and protein synthetic capabilities of asexual erythrocytic stages and sexual stages of P. falciparum.