Characterisation and sub-cellular localisation of enzymes of the DOXP pathway inPlasmodium falciparum

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In previous studies we demonstrated that in P. falciparum isoprenoids are synthesised by the 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway. This pathway was discovered only recently and had not been fully elucidated at the beginning of our work. During the first two years funding period we were able to functionally characterise the last two missing enzymes, GcpE and LytB. Both enzymes turned out to represent oxygen-sensitive [4Fe-4S] proteins. Although not fully proven, there is evidence that the biochemical reactions of the DOXP pathway may take place inside the plastid-like organelle (apicoplast) of P. falciparum. Therefore, we plan to study the sub-cellular localisation of the involved enzymes. In addition, we plan to identify additional apicoplast-resident proteins required as co-factors for the enzymatic activity of GcpE and LytB. We expect that these studies will contribute to our understanding of the metabolic functions of the apicoplast.