BRANCHED CHAIN AMINO ACID BIOSYNTHESIS IN E COLI

大肠杆菌中支链氨基酸的生物合成

• 批准号: 6332201
• 负责人: G. WESLEY HATFIELD
• 金额: $ 27.37万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332201
• 关键词: Escherichia coli; aminoacid biosynthesis; bacterial genetics; branched chain aminoacid; genetic regulation; genetic transcription; microarray technology; microorganism culture; microorganism metabolism; operon

DESCRIPTION: (Adapted from the Investigator's abstract): Our current understanding of gene regulation in Escherichia coli suggests three hierarchical levels of control: 1) global control of basal level gene expression by chromosome structure; 2) global regulatory proteinmediated control of stimulons and regulons; and, 3) operon specific controls. The first level of control is exemplified by the DNA-supercoiling-dependent mechanisms described for the coordination of basal level expression of operons of the ilv regulon. It has been shown that these controls can be influenced by the topological structure of the chromosome, and that DNA architectural proteins such as IHF are able to modulate the formation and location of these structures. The experiments described in this proposal are designed to further characterize this first level of global gene regulation. It is proposed that regulation of gene expression by chromosome structure is influenced by the energy charge of the cell, which in turn is influenced by nutritional and environmental conditions that require transitions from one growth state to another. To test this idea, computational and genomic methods will be employed. DNA arrays will be used to determine differential gene expression profiles, and cellular energy charge and DNA supercoiling levels will be monitored during aerobic to anaerobic growth transitions in the presence and absence of IHF. Computational predictions of IHF binding sites and predictions of the topological state of the E. coli chromosome will be used to analyze these data. It is expected that these experiments will identify additional operons that respond to energy charge and DNA supercoiling-mediated signals for further characterization. These experiments will further provide a wealth of information for future studies concerning the operon specific and global regulation of carbon and energy metabolism genes during aerobic to anaerobic growth transitions.

描述：（改编自研究者摘要）：我们目前的 对大肠杆菌基因调控的理解表明， 分级控制水平：1）基础水平基因的全局控制 通过染色体结构表达; 2）全局调节蛋白介导 刺激物和调节子的控制;和，3）操纵子特异性控制。第一 DNA超螺旋依赖性机制是控制水平的例证 描述了ILV操纵子基础水平表达的协调 调节子已经表明，这些控制可以受到 染色体的拓扑结构，以及DNA结构蛋白质 例如IHF能够调节这些的形成和位置， 结构.本提案中描述的实验旨在进一步 描述了第一个层次的基因调控。拟将 染色体结构对基因表达的调节受 细胞的能量负荷，这反过来又受到营养和 需要从一种生长状态过渡到 另为了验证这一想法，将采用计算和基因组方法。 DNA阵列将用于确定差异基因表达谱， 细胞能荷和DNA超螺旋水平将在 在存在和不存在IHF的情况下，需氧至厌氧生长转变。 IHF结合位点的计算预测和 E. coli染色体进行分析。 预期这些实验将鉴定出另外的操纵子， 响应能量电荷和DNA超螺旋介导的信号， 特征化这些实验将进一步提供丰富的 关于操纵子特异性和全局性的未来研究的信息 有氧到无氧过程中碳和能量代谢基因的调节 增长转型。