Metabolic Engineering Studies of Extreme Thermoacidophily

极端嗜酸代谢工程研究

• 批准号: 7943058
• 负责人: Robert M Kelly
• 金额: $ 25.74万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943058
• 关键词: Acids; Archaea; Bioenergetics; Cell membrane; Characteristics; Crenarchaeota; Cytosol; DNA Microarray Chip; Engineering; Environment; Exhibits; Gene Targeting; Gene Transfer; Genes; Genetic; Genetic Transcription; Genome; Growth; Heavy Metals; Instruction; Life; Membrane; Metabolic; Metabolism; Metallosphaera; Metals; Microbiologic Phenomena; Modeling; Molecular; Pathway Analysis; Pathway interactions; Peptides; Physiological; Physiology; Process; Proton Pump; Radiation; Resistance; Sequence Analysis; Stress; Sulfur; System; Temperature; Testing; base; carbon fixation; chromatin modification; functional genomics; insight; interest; member; microorganism; oxidation; pH gradient; pressure; tool; transcription factor

Extreme thermoacidophily (growth ~ 60¿C, pH s 3) is a remarkable growth physiology exhibited by certain members of the Crenarchaeota and Euryarchaeota, the major archaeal phyla. Interesting features of microorganisms in this group include: exploitation of large pH gradients across the cell membrane to drive proton pumping for maintaining a near neutral cytosol, resistance to normally toxic levels of base and heavy metals, capacity to grow autotrophically by fixing CO2, heterotrophically on peptides, or mixotrophically by using both modes, bioenergetics based on dissimilatory oxidation of reduced metal and sulfur species, unique membranes and S-Iayers, and growth stimulation by molecular H2¿ By strategically integrating some or all of these physiological features into cellular metabolism, life in hot acid becomes possible. However, little is known about how this happens beyond biochemical characterization of a few proteins from these microorganisms and rudimentary pathway analysis. Yet, if the mechanisms behind these features were understood, insights into the biological strategies that define extreme thermoacidophily would result. Such insights have important scientific and technological importance. For example, it is clear that the Crenarcheaota (not all of which are extreme thermoacidophiles) comprise a significant fraction of the global biomass, and are relevant beyond extreme niches. These organisms play an expanding role in global carbon cycling, nitrogen cycling, symbiosis and eukaryotic interactions. The transcriptional and translational mechanisms observed in archaea are closely related to those found in eukaryotes and, thus, provide an excellent alternative perspective. Finally, clues to cellular survival under extreme conditions could lead to interesting medical strategies for surviving stress for higher eukaryotes. The objectives of this project are: 1) Determine the components of Iithotrophic pathways in the extreme thermoacidophile Metallosphaera sedula and how these processes relate to one another and integrate into overall cellular bioenergetics; 2) Investigate the metallomics underlying M. sedula's intrinsic heavy and base metal resistance; 3) Integrate the findings gained from aims 1 and 2 with studies on transcription factors, chromatin modification, and toxin-antitoxin loci to derive a conceptual model for the M. sedula transcription regulatory system.

极端嗜热嗜酸（生长~60°C，pH s 3）是一种显着的生长生理学 由主要古菌 Crenarchaeota 和 Euryarchaeota 的某些成员展示 门。该组微生物的有趣特征包括： 利用大 pH 值 穿过细胞膜的梯度驱动质子泵送以维持接近中性 细胞质，对碱金属和重金属正常毒性水平的抵抗力，生长能力 通过固定 CO2 进行自养，通过肽进行异养，或通过同时使用两者进行混合营养 模式，基于还原金属和硫物质的异化氧化的生物能学， 独特的膜和 S 层，以及分子 H2 的生长刺激?? 将部分或全部这些生理特征整合到细胞代谢中，在热酸中生活 成为可能。然而，除了生物化学之外，人们对这种现象是如何发生的知之甚少。 来自这些微生物的一些蛋白质的表征和基本途径 分析。然而，如果了解这些特征背后的机制，就能深入了解 定义极端嗜热嗜酸的生物学策略将会产生。这样的见解有 重要的科学和技术重要性。例如，很明显， Crenarcheaota（并非所有都是极端嗜热嗜酸菌）包含重要的 全球生物量的一小部分，并且与极端利基无关。这些生物体 在全球碳循环、氮循环、共生和 真核相互作用。观察到的转录和翻译机制 古细菌与真核生物中发现的古细菌密切相关，因此提供了极好的 另类观点。最后，极端条件下细胞生存的线索可能会导致 高等真核生物生存压力的有趣医学策略。的目标 该项目是： 1) 确定极端情况下的单营养途径的组成部分 嗜热嗜酸菌 Metallosphaera sedula 以及这些过程如何相互关联以及 融入整体细胞生物能量学； 2) 研究 M 背后的金属组学。 sedula 固有的重金属和贱金属抵抗力； 3) 整合所得结果 目标 1 和 2 研究转录因子、染色质修饰和毒素-抗毒素 位点来推导 M. sedula 转录调控系统的概念模型。