Genetics and biochemistry of coenzyme A biosynthesis in the yeast Saccharomyces cerevisiae

酿酒酵母辅酶 A 生物合成的遗传学和生物化学

基本信息

项目摘要

Since coenzyme A (CoA) and its acylation products (mainly acetyl-CoA) are of central importance for metabolism in all organisms, biosynthesis of CoA is an essential cellular function. By identification of structural genes CAB1-CAB5 (coenzyme A biosynthesis) and construction of a hyperactive variant of key enzyme pantothenate kinase (CAB1 gene product) we obtained yeast cells with a concentration of acetyl-CoA which was about 6-fold increased, compared to a wild-type. Since acetyl-CoA has a fundamental role in metabolism and functions as a signalling molecule for initiation of a new cell division cycle we wish to investigate the implications of the increased amount of acetyl-CoA for the cellular proteome and part of its metabolome (focusing on fatty acids and ergosterol). By varying gene expression of genes ACS2 (acetyl-CoA synthetase) and LEU5 (mitochondrial CoA importer) we plan to modify the ratio of CoA and acetyl-CoA as well as the intracellular distribution of CoA. Results of these studies should allow us to define favourable conditions for CoA-dependent processes in biotechnology. We were able to demonstrate that gene products Cab2-Cab5 interact with each other and that they form a CoA-synthesizing protein complex (CoA-SPC) with Cab3 as a key subunit for mediating interactions. In the future we plan to investigate CoA-SPC more precisely, possibly defining subunits not yet identified and its stoichiometry. To do this, Cab3 will be epitope-tagged and used for affinity-purification of the complex which will be subsequently analyzed by mass spectrometry. Results obtained for CoA-SPC of yeast will be finally compared with the situation in higher eukaryotes.
由于辅酶A (CoA)及其酰化产物(主要是乙酰辅酶A)在所有生物体的代谢中起着至关重要的作用,因此辅酶A的生物合成是必不可少的细胞功能。通过结构基因CAB1- cab5(辅酶A生物合成)的鉴定和关键酶泛酸激酶高活性变体(CAB1基因产物)的构建,我们获得了与野生型相比乙酰辅酶A浓度增加约6倍的酵母细胞。由于乙酰辅酶a在代谢中具有基础作用,并作为启动新细胞分裂周期的信号分子,我们希望研究乙酰辅酶a含量增加对细胞蛋白质组及其部分代谢组(重点是脂肪酸和麦角甾醇)的影响。通过改变ACS2(乙酰辅酶a合成酶)和LEU5(线粒体辅酶a输入源)基因的表达,我们计划改变辅酶a和乙酰辅酶a的比例以及辅酶a在细胞内的分布。这些研究的结果应该使我们能够确定生物技术中辅酶a依赖过程的有利条件。我们能够证明基因产物Cab2-Cab5彼此相互作用,并且它们形成coa合成蛋白复合物(CoA-SPC),其中Cab3作为介导相互作用的关键亚基。在未来,我们计划更精确地研究CoA-SPC,可能定义尚未确定的亚基及其化学计量学。为了做到这一点,Cab3将被表位标记并用于复合物的亲和纯化,随后将通过质谱分析。最后将酵母中辅酶a - spc的测定结果与高等真核生物进行比较。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genetic analysis of coenzyme A biosynthesis in the yeast Saccharomyces cerevisiae: identification of a conditional mutation in the pantothenate kinase gene CAB1
  • DOI:
    10.1007/s00294-009-0234-1
  • 发表时间:
    2009-04-01
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Olzhausen, Judith;Schuebbe, Sabrina;Schueller, Hans-Joachim
  • 通讯作者:
    Schueller, Hans-Joachim
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Professor Dr. Hans-Joachim Schüller其他文献

Professor Dr. Hans-Joachim Schüller的其他文献

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{{ truncateString('Professor Dr. Hans-Joachim Schüller', 18)}}的其他基金

Regulated gene activation and chromatin modification of structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae
酿酒酵母磷脂生物合成结构基因的调控基因激活和染色质修饰
  • 批准号:
    5259840
  • 财政年份:
    2000
  • 资助金额:
    --
  • 项目类别:
    Research Grants

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