Apicomplexan parasites possess distinct nuclear-encoded, but apicoplast-localized, plant-type ferredoxin-NADP(+) reductase and ferredoxin

In searching for nuclear-encoded, apicoplast-localized proteins we have clo ned ferredoxin-NADP(+) reductase from Toxoplasma gondii and a [2Fe-2S] ferr edoxin from Plasmodium falciparum. This chloroplast-localized redox system has been extensively studied in photosynthetic organisms and is responsible for the electron transfer from photosystem I to NADP(+). Besides this ligh t-dependent reaction in nonphotosynthetic plastids (e.g. from roots), elect rons can also flow in the reverse direction, from NADPH to ferredoxin, whic h then serves as an important reductant for various plastid-localized enzym es. These plastids possess related, but distinct, ferredoxin-NADP(+) reduct ase and ferredoxin isoforms for this purpose. We provide phylogenetic evide nce that the T. gondii reductase is similar to such nonphotosynthetic isofo rms. Both the P. falciparum [2Fe-2S] ferredoxin and the T. gondii ferredoxi n-NADP(+) reductase possess an N-terminal bipartite transit peptide domain typical for apicoplast-localized proteins. The recombinant proteins were ob tained in active form, and antibodies raised against the reductase recogniz ed two bands on Western blots of T. gondii tachyzoite lysates, indicative o f the unprocessed and native form, respectively. We propose that the role o f this redox system is to provide reduced ferredoxin, which might then be u sed for fatty acid desaturation or other biosynthetic processes yet to be d efined. Thus, the interaction of these two proteins offers an attractive ta rget for drug intervention.