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

在以前的研究中，我们证明在恶性疟原虫中，类异戊二烯是通过1-脱氧-D-5-磷酸木糖(DOXP)途径合成的。这一途径是最近才发现的，在我们工作开始时还没有完全阐明。在前两年的资助期内，我们能够对最后两种缺失的酶GcpE和LytB进行功能鉴定。事实证明，这两种酶都代表对氧敏感的[4Fe-4S]蛋白质。尽管没有得到充分的证实，但有证据表明DOXP途径的生化反应可能发生在恶性疟原虫的类质体细胞器(质膜)内。因此，我们计划研究相关酶的亚细胞定位。此外，我们计划确定更多的作为GcpE和LytB酶活性辅助因子所需的质膜驻留蛋白。我们期望这些研究将有助于我们理解质外体的代谢功能。

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.