Gurvitz Aner
Section of Physiology of Lipid Metabolism, Center for Physiology, Pathophysiology and Immunology, Institute of Physiology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
J Biomed Biotechnol. 2009;2009:950864. doi: 10.1155/2009/950864. Epub 2010 Jan 21.
Leishmania major causes leishmaniasis and is grouped within the Trypanosomatidae family, which also includes the etiologic agent for African sleeping sickness, Trypanosoma brucei. Previous studies on T. brucei showed that acyl carrier protein (ACP) of mitochondrial fatty acid synthase type 2 (FASII) plays a crucial role in parasite survival. Additionally, 3-oxoacyl-ACP synthase TbKASIII as well as TbHTD2 representing 3-hydroxyacyl-ACP dehydratase were also identified; however, 3-oxoacyl-ACP reductase TbKAR1 has hitherto evaded positive identification. Here, potential Leishmania FASII components LmjF07.0440 and LmjF07.0430 were revealed as 3-hydroxyacyl-ACP dehydratases LmHTD2-1 and LmHTD2-2, respectively, whereas LmjF27.2440 was identified as LmKAR1. These Leishmania proteins were ectopically expressed in Saccharomyces cerevisiae htd2Delta or oar1Delta respiratory deficient cells lacking the corresponding mitochondrial FASII enzymes Htd2p and Oar1p. Yeast mutants producing mitochondrially targeted versions of the parasite proteins resembled the self-complemented cells for respiratory growth. This is the first identification of a FASII-like 3-oxoacyl-ACP reductase from a kinetoplastid parasite.
硕大利什曼原虫可引发利什曼病，它属于锥虫科，该科还包括非洲昏睡病的病原体布氏锥虫。先前对布氏锥虫的研究表明，线粒体脂肪酸合酶2型（FASII）的酰基载体蛋白（ACP）在寄生虫存活中起着关键作用。此外，还鉴定出了3-氧代酰基-ACP合酶TbKASIII以及代表3-羟基酰基-ACP脱水酶的TbHTD2；然而，3-氧代酰基-ACP还原酶TbKAR1迄今尚未得到阳性鉴定。在此，潜在的利什曼原虫FASII组分LmjF07.0440和LmjF07.0430分别被揭示为3-羟基酰基-ACP脱水酶LmHTD2-1和LmHTD2-2，而LmjF27.2440被鉴定为LmKAR1。这些利什曼原虫蛋白在缺乏相应线粒体FASII酶Htd2p和Oar1p的酿酒酵母htd2Δ或oar1Δ呼吸缺陷细胞中异位表达。产生寄生虫蛋白线粒体靶向版本的酵母突变体在呼吸生长方面类似于自我互补细胞。这是首次从动基体寄生虫中鉴定出一种类似FASII的3-氧代酰基-ACP还原酶。
