Carotenoid Biosynthesis in Intraerythrocytic Stages of Plasmodium falciparum
Carotenoid Biosynthesis in Intraerythrocytic Stages of Plasmodium falciparum
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DOI：
10.1074/jbc.m807464200
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发表时间：
2009-04-10
影响因子：
4.8
通讯作者：
Katzin, Alejandro M.
中科院分区：
文献类型：
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作者：
Tonhosolo, Renata;D'Alexandri, Fabio L.;Katzin, Alejandro M.
类胡萝卜素是一种广泛存在的亲脂性色素，由所有光合生物和一些非光合真菌和细菌合成。所有类胡萝卜素都来源于C40类异戊二烯前体香叶基香叶基焦磷酸，它们的化学和物理性质与光吸收，自由基清除和抗氧化活性有关。类胡萝卜素通常在定义明确的亚细胞器质体中合成，质体也存在于顶复门中，顶复门包括许多重要的人类寄生虫，如疟原虫和弓形虫。最近的研究表明，弓形虫可以合成脱落酸。因此，我们想知道恶性疟原虫是否也能够合成类胡萝卜素。在此，生化研究结果表明，类胡萝卜素的生物合成存在于红细胞内阶段的顶复形寄生虫恶性疟原虫。利用放射性同位素代谢标记技术，用植物类胡萝卜素生物合成的特异性抑制剂氟草松进行体外抑制试验，结果表明，恶性疟原虫红细胞内期可合成类胡萝卜素化合物。还鉴定和表征了呈现八氢番茄红素合酶活性的疟原虫酶。这些发现不仅有助于目前对恶性疟原虫进化的理解，而且揭示了一种可能作为化疗靶点的途径。
Carotenoids are widespread lipophilic pigments synthesized by all photosynthetic organisms and some nonphotosynthetic fungi and bacteria. All carotenoids are derived from the C40 isoprenoid precursor geranylgeranyl pyrophosphate, and their chemical and physical properties are associated with light absorption, free radical scavenging, and antioxidant activity. Carotenoids are generally synthesized in well defined subcellular organelles, the plastids, which are also present in the phylum Apicomplexa, which comprises a number of important human parasites, such as Plasmodium and Toxoplasma. Recently, it was demonstrated that Toxoplasma gondii synthesizes abscisic acid. We therefore asked if Plasmodium falciparum is also capable of synthesizing carotenoids. Herein, biochemical findings demonstrated the presence of carotenoid biosynthesis in the intraerythrocytic stages of the apicomplexan parasite P. falciparum. Using metabolic labeling with radioisotopes, in vitro inhibition tests with norflurazon, a specific inhibitor of plant carotenoid biosynthesis, the results showed that intraerythrocytic stages of P. falciparum synthesize carotenoid compounds. A plasmodial enzyme that presented phytoene synthase activity was also identified and characterized. These findings not only contribute to the current understanding of P. falciparum evolution but shed light on a pathway that could serve as a chemotherapeutic target.