Syriopoulos C, Panayotarou A, Lai K, Klapa Maria I
Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering and High-Temperature Chemical Processes (ICE-HT), Foundation for Research and Technology-Hellas (FORTH), GR-26504 Patras, Greece.
Mol Biosyst. 2008 Sep;4(9):937-49. doi: 10.1039/b718732g. Epub 2008 Jul 4.
Despite being extensively studied in various organisms due to scientific, industrial and medical interest, the galactose assimilation function and regulation, and especially its interaction with other parts of cellular physiology, have not been fully elucidated yet. The post-genomic era holistic techniques ("omics") could assist towards this goal. In this paper, we holistically analyzed full-genome Saccharomyces cerevisiae transcriptional profiling data concerning its glucose- and galactose-grown wild-type (WT) physiology and its glucose-grown gal7-deficient (GAL7Delta) physiology, as these were obtained in the experiment described in Lai and Elsas (Biochem. Biophys. Res. Commun. 2000, 271, 392-400). The gal7 gene encodes for the second enzyme of the galactose assimilation, Leloir, pathway, and its deficiency in humans causes a potentially lethal disease, named "classic galactosemia". Analysis of the galactose-grown compared to the glucose-grown WT physiology indicated a significant increase in the transcriptional expression of the ribosomal machinery and decrease in the transcriptional activity of the fatty acids' beta-oxidation at the peroxisomes. Comparison of GAL7Delta to WT physiology in glucose indicated a significant transcriptional increase in the mitochondrial activity and the rate of catabolism of disaccharides, including sucrose, mannose and trehalose, towards amplified biosynthesis of the main cell wall components. Comparison with other physiological conditions indicated strong correlation between the glucose-grown GAL7Delta transcriptional physiology and the WT growth under glucose derepression conditions. Finally, the acquired results and the large number of still unknown genes that were related to the galactose assimilation regulation indicated the need for further, specifically designed, perturbations and integrated analyses of multiple levels of cellular function.
尽管由于科学、工业和医学方面的兴趣,半乳糖同化功能及其调控,尤其是其与细胞生理学其他部分的相互作用,在各种生物体中都得到了广泛研究,但尚未完全阐明。后基因组时代的整体技术(“组学”)有助于实现这一目标。在本文中,我们全面分析了酿酒酵母全基因组转录谱数据,这些数据涉及葡萄糖和半乳糖培养的野生型(WT)生理学以及葡萄糖培养的gal7缺陷型(GAL7Delta)生理学,这些数据是在Lai和Elsas(《生物化学与生物物理研究通讯》2000年,271卷,392 - 400页)所述的实验中获得的。gal7基因编码半乳糖同化Leloir途径的第二种酶,其在人类中的缺陷会导致一种潜在致命疾病,即“经典半乳糖血症”。与葡萄糖培养的WT生理学相比,半乳糖培养的WT生理学分析表明核糖体机制的转录表达显著增加,而过氧化物酶体中脂肪酸β - 氧化的转录活性降低。在葡萄糖中GAL7Delta与WT生理学的比较表明,线粒体活性以及包括蔗糖、甘露糖和海藻糖在内的二糖分解代谢速率显著转录增加,以促进主要细胞壁成分的生物合成扩增。与其他生理条件的比较表明,葡萄糖培养的GAL7Delta转录生理学与葡萄糖去阻遏条件下的WT生长之间存在强相关性。最后,所获得的结果以及与半乳糖同化调控相关的大量仍未知的基因表明,需要进一步进行专门设计的扰动以及对细胞功能多个层面的综合分析。