Polyamine and Arginine Metabolism in Pseudomonas aeruginosa

多胺(腐胺、亚精胺和精胺)是所有生物体中发现的主要有机聚阳离子。它们在细胞生长中发挥着重要的生物学作用，但人们对此知之甚少，包括DNA和RNA的生物合成以及防止DNA损伤。多胺代谢的复杂性从它与精氨酸代谢网络的紧密联系中得到了证明，这一点从以前资助的项目的转录组分析中得到了证明。精氨酸分解代谢在铜绿假单胞菌生理中的重要性体现在精氨酸作为碳、氮和能量的唯一来源的四条不寻常的分解代谢途径中。这项研究的目的是描述多胺和精氨酸的代谢途径以及控制这些化合物的代谢过程的机制。铜绿假单胞菌是一种很好的模式生物，因为它可以非常有效地利用这些化合物作为碳和氮的唯一来源。本项目的具体目标是：(I)阐明基本的多胺分解代谢途径及其调控；(Ii)表征两种精氨酸分解代谢途径及其与多胺代谢的联系。这些将通过使用转录图谱分析、计算机辅助数据挖掘、遗传操作以及酶的纯化和表征来实现。这项研究将在生化和遗传学水平上为多胺和精氨酸代谢网络的运行和调节提供基本的见解。许多目前未知的基因的生化和生理功能的分配将适用于其他细菌。本项目采用的实验方法为未来细菌生理学研究中的数据挖掘/集成提供了一个完美的范例。广泛的影响：本研究的发现将提供有关多胺和精氨酸代谢的新的和有意义的信息，这些信息可能对生物学和农业的多个领域有益。参与该项目的研究生和本科生将接受遗传学、生物化学和生物信息学的跨学科培训，从而形成对细菌代谢生物化学和调控的综合看法。同样类型的培训已被整合到为高年级本科生和硕士研究生开设的实验室课程中。此外，这些训练有素的研究生将有机会参与由国家科学基金会支持的佐治亚州立大学的BioBus项目，以推广K12教育。

Polyamines (putrescine, spermidine, and spermine) are the major organic polycations found in all living organisms. They play an essential but poorly understood biological role in cell growth, including the biosynthesis of DNA and RNA and protection from DNA damage. The complexity of polyamine metabolism is evidenced by its tight link to the metabolic network for arginine, as evidenced by transcriptome analysis from previously funded projects. The significance of arginine catabolism in the physiology of Pseudomonas aeruginosa is reflected in the unusual presence of four catabolic pathways for arginine utilization as the sole source of carbon, nitrogen, and energy. The goal of this research is to characterize the metabolic pathways of polyamines and arginine and the mechanisms controlling the metabolic processes of these compounds. P. aeruginosa serves as an excellent model organism since it can utilize these compounds very efficiently as the sole source of carbon and nitrogen. The specific aims of this project are: (i) to elucidate the fundamental polyamine catabolic pathways and their regulation; and (ii) to characterize two arginine catabolic pathways and their linkages to polyamine metabolism. These will be accomplished through the use of transcriptional profiling analyses, computer-aided data mining, genetics manipulation, and enzyme purification and characterization. This research will provide fundamental insights into the operation and regulation of polyamines and arginine metabolic networks at the biochemical and genetics levels. The assignments of biochemical and physiological functions to many currently unknown genes will be applicable to other bacteria. The experimental approaches employed in this project provide a perfect example for data mining/integration in future studies in bacterial physiology.Broader impacts: Findings from this research will provide novel and significant information on polyamines and arginine metabolism that could be beneficial to several fields of biology and agriculture. Graduate students as well as undergraduate students, who participate in this project, will receive cross-disciplinary training in genetics, biochemistry, and bioinformatics, and thus developing an integrative view of metabolic biochemistry and regulation in bacteria. The same type of training has been integrated into a laboratory course for the senior undergraduate and MS graduate students. Further, these trained graduate students will have the opportunity to involve in the BioBus project supported by NSF to Georgia State University for the outreach effort to the K12 education.