必需的分枝杆菌基因 fabG1 和 fabG4 编码 3-氧代酰基硫酯还原酶，在酵母线粒体脂肪酸合酶 2 型中起作用。,Molecular Genetics and Genomics

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必需的分枝杆菌基因 fabG1 和 fabG4 编码 3-氧代酰基硫酯还原酶，在酵母线粒体脂肪酸合酶 2 型中起作用。
Molecular Genetics and Genomics ( IF 2.3 ) Pub Date : 2009-08-14 , DOI: 10.1007/s00438-009-0474-2
Aner Gurvitz ₁

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结核分枝杆菌对全世界人类健康构成严重威胁。因此，重要的是扩大我们对重要分枝杆菌过程的了解，例如受 2 型脂肪酸合酶 (FASII) 影响的过程，以及发现新的过程。分枝杆菌 FASII 进行分枝杆菌酸生物合成，这依赖于一组必需酶，包括 3-氧代酰基-AcpM 还原酶 FabG1/Rv1483。然而，结核分枝杆菌基因组编码四个额外的 FabG 同源物，称为 FabG2-FabG5，其功能迄今尚未详细表征。在四个候选者中，FabG4/Rv0242c 最近被证明对牛分枝杆菌 BCG 的生存至关重要。目前的工作是通过评估缺乏线粒体 3-氧代酰基-ACP 还原酶活性的酵母 oar1Delta 突变细胞作为替代系统来表达针对线粒体的 FabG1/MabA 的适用性而启动的。产生这种靶向 FabG1 变体的突变酵母细胞对于所有记录的表型特征基本上都是野生型，包括在甘油培养基上的呼吸生长、细胞色素组装和类脂酸生产。这表明在酵母线粒体从头脂肪酸生物合成的框架内，FabG1 能够在 M.结核。此后，FabG2-FabG5 在 oar1Delta 菌株中表达为线粒体蛋白，和 FabG4 被发现补充突变表型并含有高水平的 3-氧代酰基硫酯还原酶活性。因此，与 FabG1 一样，FabG4 也是一种必不可少的生理功能 3-氧代酰基硫酯还原酶，尽管后者与分枝杆菌 FASII 的关系仍有待探索。

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The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-thioester reductases that are functional in yeast mitochondrial fatty acid synthase type 2.

Mycobacterium tuberculosis represents a severe threat to human health worldwide. Therefore, it is important to expand our knowledge of vital mycobacterial processes, such as that effected by fatty acid synthase type 2 (FASII), as well as to uncover novel ones. Mycobacterial FASII undertakes mycolic acid biosynthesis, which relies on a set of essential enzymes, including 3-oxoacyl-AcpM reductase FabG1/Rv1483. However, the M. tuberculosis genome encodes four additional FabG homologs, designated FabG2-FabG5, whose functions have hitherto not been characterized in detail. Of the four candidates, FabG4/Rv0242c was recently shown to be essential for the survival of M. bovis BCG. The present work was initiated by assessing the suitability of yeast oar1Delta mutant cells lacking mitochondrial 3-oxoacyl-ACP reductase activity to act as a surrogate system for expressing FabG1/MabA directed to the mitochondria. Mutant yeast cells producing this targeted FabG1 variant were essentially wild type for all of the chronicled phenotype characteristics, including respiratory growth on glycerol medium, cytochrome assembly and lipoid acid production. This indicated that within the framework of de novo fatty acid biosynthesis in yeast mitochondria, FabG1 was able to act on shorter (C(4)) acyl substrates than was previously proposed (C(8-20)) during mycolic acid biosynthesis in M. tuberculosis. Thereafter, FabG2-FabG5 were expressed as mitochondrial proteins in the oar1Delta strain, and FabG4 was found to complement the mutant phenotype and contain high levels of 3-oxoacyl-thioester reductase activity. Hence, like FabG1, FabG4 is also an essential, physiologically functional 3-oxoacyl-thioester reductase, albeit the latter's involvement in mycobacterial FASII remains to be explored.

更新日期：2019-11-01

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