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克氏锥虫多胺代谢:参与多胺生物合成的异源基因表达和调控的研究。

Polyamine metabolism in Trypanosoma cruzi: studies on the expression and regulation of heterologous genes involved in polyamine biosynthesis.

机构信息

Fundación Instituto Leloir, Ave. Patricias Argentinas 435, 1405, Buenos Aires, Argentina.

出版信息

Amino Acids. 2010 Feb;38(2):645-51. doi: 10.1007/s00726-009-0425-6. Epub 2009 Dec 3.

Abstract

Biochemical studies have shown that Trypanosoma cruzi and Toxoplasma gondii are the only eukaryotic organisms so far described which are auxotrophic for polyamines. Both parasites are unable to carry out the de novo biosynthesis of putrescine, and therefore they need the addition of exogenous polyamines to the culture medium for their normal proliferation. Further investigations at the molecular level have demonstrated that the wild-type T. cruzi genome does not contain ornithine or arginine decarboxylase-like nucleic acid sequences, and that the corresponding genes have been presumably lost during evolution. Since T. cruzi behaves as a deletion mutant for ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) genes, this parasite has been selected to study the regulation of the expression of heterologous genes involved in polyamine biosynthesis in other organisms. The resulting transgenic parasites have been useful tools to analyze the different stages of gene expression after transformation, as well as the mechanisms of drug resistance induction and the post-translational processing of enzyme precursors.

摘要

生化研究表明,克氏锥虫和刚地弓形虫是迄今为止仅有的两种对多胺呈营养缺陷型的真核生物。这两种寄生虫都不能从头合成腐胺,因此它们需要在培养基中添加外源多胺才能正常增殖。在分子水平上的进一步研究表明,野生型克氏锥虫基因组不含有鸟氨酸或精氨酸脱羧酶样核酸序列,相应的基因在进化过程中可能已经丢失。由于克氏锥虫表现为鸟氨酸脱羧酶(ODC)和精氨酸脱羧酶(ADC)基因的缺失突变体,因此该寄生虫已被选中用于研究参与其他生物体多胺生物合成的异源基因表达的调控。由此产生的转基因寄生虫是分析转化后基因表达不同阶段、诱导耐药性的机制以及酶前体的翻译后加工的有用工具。

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