Plant-type trehalose synthetic pathway in cryptosporidium and some other apicomplexans.
Plant-type trehalose synthetic pathway in cryptosporidium and some other apicomplexans.
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DOI：
10.1371/journal.pone.0012593
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发表时间：
2010-09-07
期刊：
影响因子：
3.7
通讯作者：
Zhu G
中科院分区：
文献类型：
--
作者：
Yu Y;Zhang H;Zhu G
海藻糖合成途径存在于细菌、真菌、植物和无脊椎动物中，但不存在于脊椎动物中。这种双糖的主要作用是作为一种抗干燥、热、冷和氧化的应激保护剂。参与海藻糖合成的基因已在顶复合体寄生虫中观察到，但对这些酶知之甚少。研究顶复合体中海藻糖的合成不仅可以为这一途径的进化提供新的思路，还可以为探索这一途径作为新的药物靶点提供数据。我们观察到海藻糖合成途径存在于隐孢子虫和其他顶复合体和肺泡虫中。海藻糖6-磷酸合成酶[T6PS； EC 2.4.1.15]和海藻糖磷酸酶[TPase； EC 3.1.3.12]这两个关键酶作为II类双功能蛋白（T6PS-TPase）存在于除疟原虫外的大多数顶端复合体中。合成前体（udp -葡萄糖）的酶与双底物udp -半乳糖/葡萄糖焦磷酸化酶（UGGPases）同源，而不是“经典”的udp -葡萄糖焦磷酸化酶（UGPase）。系统发育重建表明，顶复合体和其他肺泡动物的t6ps - tpase和uggpase在进化上都与层桩和植物有关。在卵囊形成前或卵囊形成过程中，小虫卵胞内发育晚期T6PS-TPase的表达水平高度升高，这表明海藻糖可能在卵囊中作为一种抗环境胁迫的重要保护剂。最后，在小虫卵囊中检测到海藻糖，证实了小虫卵囊中海藻糖的合成活性。在包括隐孢子虫在内的大多数顶复合体寄生虫中都有海藻糖合成途径，并且在小隐孢子虫卵囊中证实了海藻糖的存在。该通路中的关键酶（即T6PS-TPase和UGGPase）是植物型的，在人类和动物中不存在，可能作为顶复合体的新药物靶点。
The trehalose synthetic pathway is present in bacteria, fungi, plants and invertebrate animals, but is absent in vertebrates. This disaccharide mainly functions as a stress protectant against desiccation, heat, cold and oxidation. Genes involved in trehalose synthesis have been observed in apicomplexan parasites, but little was known about these enzymes. Study on trehalose synthesis in apicomplexans would not only shed new light into the evolution of this pathway, but also provide data for exploring this pathway as novel drug target. We have observed the presence of the trehalose synthetic pathway in Cryptosporidium and other apicomplexans and alveolates. Two key enzymes (trehalose 6-phosphate synthase [T6PS; EC 2.4.1.15] and trehalose phosphatase [TPase; EC 3.1.3.12] are present as Class II bifunctional proteins (T6PS-TPase) in the majority of apicomplexans with the exception of Plasmodium species. The enzyme for synthesizing the precursor (UDP-glucose) is homologous to dual-substrate UDP-galactose/glucose pyrophosphorylases (UGGPases), rather than the “classic” UDP-glucose pyrophosphorylase (UGPase). Phylogenetic recontructions indicate that both T6PS-TPases and UGGPases in apicomplexans and other alveolates are evolutionarily affiliated with stramenopiles and plants. The expression level of T6PS-TPase in C. parvum is highly elevated in the late intracellular developmental stage prior to or during the production of oocysts, implying that trehalose may be important in oocysts as a protectant against environmental stresses. Finally, trehalose has been detected in C. parvum oocysts, thus confirming the trehalose synthetic activity in this parasite. A trehalose synthetic pathway is described in the majority of apicomplexan parasites including Cryptosporidium and the presence of trehalose was confirmed in the C. parvum oocyst. Key enzymes in the pathway (i.e., T6PS-TPase and UGGPase) are plant-type and absent in humans and animals, and may potentially serve as novel drug targets in the apicomplexans.
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