Metabolism of sulfur amino acids in Saccharomyces cerevisiae
Metabolism of sulfur amino acids in Saccharomyces cerevisiae
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DOI：
10.1128/mmbr.61.4.503-532.1997
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发表时间：
1997-12
影响因子：
12.9
通讯作者：
Dominique Thomas;Y. Surdin-Kerjan
中科院分区：
文献类型：
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作者：
Dominique Thomas;Y. Surdin-Kerjan
含硫氨基酸在酿酒酵母中的生物合成涉及蛋氨酸和半胱氨酸的从头生物合成以及有机硫代谢产物的再循环所需的大量酶。本文综述了这些过程的细节，并分析了在这一代谢领域已获得的分子数据。硫的生物化学似乎并不是陆地生命所独有的，S。酿酒酵母是具有大量硫代谢酶的硫酸盐同化生物物种之一。审查还涉及几种酶的缺陷，导致有机硫的营养需求，虽然它们不对应的生物合成途径内的缺陷。In S.在酿酒酵母中，含硫氨基酸生物合成途径受到严格控制：响应于细胞内S-腺苷甲硫氨酸（S-腺苷蛋氨酸）量的增加，共调节基因的转录被关闭。评论的第二部分致力于这种调节的分子机制。协调反应，以蛋氨酸需要两个顺式作用的启动子元件。一个以TCACGTG序列为中心，它也构成了所有S的组分。酿酒酵母着丝粒。位于硫基因的上游，该元件是由碱性螺旋-环-螺旋因子Cbf 1 p和两个碱性亮氨酸拉链因子Met 4p和Met 28 p组成的转录激活复合物的结合位点。分子研究已经揭示了Cbf 1 p-Met 4p-Met 28 p复合物的每个亚基的特定功能以及其在DNA上组装的方式。Cbf 1 p-Met 4p-Met 28 p复合物仅包含一个转录激活模块，Met 4p亚基。Met 4p的详细突变分析阐明了其功能组织。除了其激活和bZIP结构域之外，Met 4p还包含两个调节结构域，称为抑制区和辅助结构域。当细胞内Met的水平增加时，Met 4的转录激活功能被Met 30 p阻止，Met 30 p结合到Met 4抑制区。除了Cbf 1 p-Met 4p-Met 28 p复合物外，转录调控还涉及两种含锌指蛋白Met 31 p和Met 32 p。含硫氨基酸途径的AMMET介导的控制说明了真核细胞将基因表达与代谢变化偶联的分子策略。
Sulfur amino acid biosynthesis in Saccharomyces cerevisiae involves a large number of enzymes required for the de novo biosynthesis of methionine and cysteine and the recycling of organic sulfur metabolites. This review summarizes the details of these processes and analyzes the molecular data which have been acquired in this metabolic area. Sulfur biochemistry appears not to be unique through terrestrial life, and S. cerevisiae is one of the species of sulfate-assimilatory organisms possessing a larger set of enzymes for sulfur metabolism. The review also deals with several enzyme deficiencies that lead to a nutritional requirement for organic sulfur, although they do not correspond to defects within the biosynthetic pathway. In S. cerevisiae, the sulfur amino acid biosynthetic pathway is tightly controlled: in response to an increase in the amount of intracellular S-adenosylmethionine (AdoMet), transcription of the coregulated genes is turned off. The second part of the review is devoted to the molecular mechanisms underlying this regulation. The coordinated response to AdoMet requires two cis-acting promoter elements. One centers on the sequence TCACGTG, which also constitutes a component of all S. cerevisiae centromeres. Situated upstream of the sulfur genes, this element is the binding site of a transcription activation complex consisting of a basic helix-loop-helix factor, Cbf1p, and two basic leucine zipper factors, Met4p and Met28p. Molecular studies have unraveled the specific functions for each subunit of the Cbf1p-Met4p-Met28p complex as well as the modalities of its assembly on the DNA. The Cbf1p-Met4p-Met28p complex contains only one transcription activation module, the Met4p subunit. Detailed mutational analysis of Met4p has elucidated its functional organization. In addition to its activation and bZIP domains, Met4p contains two regulatory domains, called the inhibitory region and the auxiliary domain. When the level of intracellular AdoMet increases, the transcription activation function of Met4 is prevented by Met30p, which binds to the Met4 inhibitory region. In addition to the Cbf1p-Met4p-Met28p complex, transcriptional regulation involves two zinc finger-containing proteins, Met31p and Met32p. The AdoMet-mediated control of the sulfur amino acid pathway illustrates the molecular strategies used by eucaryotic cells to couple gene expression to metabolic changes.