GENETIC CONTROL OF HEME SYNTHESIS IN S. TYPHIMURIUM

鼠伤寒沙门氏菌血红素合成的基因控制

• 批准号: 3297888
• 负责人: THOMAS EDWARD ELLIOTT
• 金额: $ 16.9万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3297888
• 关键词: 5 aminolevulinate synthase; Salmonella typhimurium; anaerobiosis; bacterial genetics; chimeric proteins; enteric bacteria; enzyme mechanism; fermentation; gene expression; genetic mapping; genetic promoter element; genetic regulation; genetic regulatory element; heme; immunoprecipitation; lac operon; microorganism metabolism; molecular cloning; mutant; nucleic acid sequence; porphyrin biosynthesis; radiotracer; starvation; superoxide dismutase

Heme serves Salmonella typhimurium as the cofactor both for cytochromes (required for respiration) and for catalase (involved in defense against oxygen's toxic effects). In S. typhimurium, the heme pathway also leads to siroheme and to vitamin B 12, which is an essential nutrient for humans. Surprisingly, very little is known about the regulation of this branched pathway in enteric bacteria. Since S. typhimurium well-suited to genetic analysis, we propose a primarily genetic approach to understanding the control of heme synthesis. We have been investigating the role of the hemA and hemL genes in the synthesis of ALA, the first committed, stable intermediate in the heme pathway. We have also identified a large number of hem mutants, and characterized the genes so defined. Here we concentrate on three specific systems chosen to illuminate different aspects of heme regulation. The hemA gene encodes the first enzyme specific to the heme pathway, glutamyl tRNA reductase. We are studying control of hemA gene expression during starvation for heme and in different growth conditions. We've also discovered a pair of genes, hemF and hemN, that encode alternative aerobic and anaerobic enzymes for a late step in heme synthesis, and we'll study the influence of oxygen on these genes. Finally, we've learned that S. typhimurium has two routes of ALA synthesis, and we suspect that this duality is important in regulating flow through the pathway to different end products. This study is also relevant to the larger problem of S. typhimurium's life in the colon. Most of what we know about enteric bacteria has been observed during growth in air. As a facultative anaerobe, S. typhimurium respires to electron acceptors when they are present, but can also grow by fermentation in their absence. In nature, electron acceptors may be present only intermittently (in the diet, or as oxygen diffusing from the epithelial surface). The ability for rapid development of respiratory capacity may be very important. We'll attempt to exploit heme regulation as an approach to more general questions about control of gene function by oxygen.

血红素作为鼠伤寒沙门氏菌的辅因子， （呼吸所需）和过氧化氢酶（参与防御 氧气的毒性作用）。 In S.鼠伤寒沙门氏菌，血红素途径也导致 到西罗血红素和维生素B 12，维生素B 12是人类的必需营养素。 令人惊讶的是，很少有人知道这个分支的调控 肠道细菌的途径。 自S.鼠伤寒沙门氏菌非常适合遗传 分析，我们提出了一个主要的遗传方法来理解 控制血红素合成。 我们一直在研究hemA和hemL基因在肿瘤发生中的作用。 ALA的合成，ALA是血红素中第一个稳定的中间体 通路 我们还发现了大量的hem突变体， 如此定义的基因的特征。 在这里，我们集中在三个具体的 系统选择照亮血红素调节的不同方面。 的 hemA基因编码血红素途径的第一种特异性酶，谷氨酰 tRNA还原酶。 我们正在研究控制hemA基因的表达， 饥饿对血红素和不同生长条件的影响。 我们还 发现了一对基因hemF和hemN，它们编码交替有氧代谢， 和厌氧酶在血红素合成的后期，我们将研究 氧气对这些基因的影响 最后，我们了解到S。 鼠伤寒沙门氏菌有两条合成ALA的途径，我们怀疑这一点。 二元性在调节通过不同途径的流动方面是重要的 最终产品。 这一研究也与S.鼠伤寒的生活 在结肠。 我们对肠道细菌的了解大部分都是 在空气中生长时观察到的。 S.是一种兼性厌氧生物。鼠伤寒 当电子受体存在时，它们会呼吸，但也可以通过 发酵在他们的缺席。 在自然界中，电子受体可以是 仅间歇性地存在（在饮食中，或作为氧气从 上皮表面）。 快速发展呼吸道疾病的能力 能力可能非常重要。 我们将尝试利用血红素调节 作为一种方法，更普遍的问题，控制基因功能， 氧气