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.
