Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum

Abstract 

In the malaria parasite Plasmodium falciparum isoprenoid precursors are synthesised inside a plastid-like organelle (apicoplast) by the mevalonate independent 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway. The last reaction step of the DOXP pathway is catalysed by the LytB enzyme which contains a [4Fe–4S] cluster. In this study, LytB of P. falciparum was shown to be catalytically active in the presence of an NADPH dependent electron transfer system comprising ferredoxin and ferredoxin-NADP⁺ reductase. LytB and ferredoxin were found to form a stable protein complex. These data suggest that the ferredoxin/ferredoxin-NADP⁺ reductase redox system serves as the physiological electron donor for LytB in the apicoplast of P. falciparum.

Abbreviations: DMAPP, dimethylallyl diphosphate, DOXP, 1-deoxy-d-xylulose-5-phosphate, Fd, ferredoxin, FNR, ferredoxin-NADP⁺ reductase, HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, IPP, isopentenyl diphosphate

Keywords: Malaria, Apicoplast, Isoprenoid biosynthesis, Ferredoxin, Iron–sulphur cluster