Quantitative Analysis of Metabolic Networks and Flux Dynamics in Thermophilic Bacteria

嗜热嗜热菌是生产生物燃料和其他有用生物化学品的潜在宿主细菌。然而，人们对其新陈代谢和代谢活动的调节知之甚少。这个项目将描述这种有机体的代谢网络，并使用经典的稳态技术来量化其代谢流量表型。此外，将开发用于动态代谢通量分析和代谢网络阐明的技术，需要基于13C同位素分析和串联质谱学的新工具和方法。该项目将1)开发一种新的动态代谢流量分析方法，2)提供验证代谢网络模型的改进技术，3)确定嗜热链霉菌的最佳生长条件。更广泛的影响：该项目承诺在代谢网络分析方面向前迈出重要的一步，这将广泛适用于许多具有生物技术和生物医学重要性的生物。此外，该项目为研究生和本科生提供了在跨学科环境中进行教育和培训的独特机会，该环境包括计算和实验生物学、代谢通量分析、质谱学和代谢网络建模。

Thermus thermophilus is a potential host bacterium for the production of biofuels and other useful biochemicals. However, relatively little is known about its metabolism and the regulation of its metabolic activity. This project will characterize the metabolic network of this organism and quantify its metabolic flux phenotypes using classical steady-state techniques. In addition, techniques will be developed for dynamic metabolic flux analysis and metabolic network elucidation, requiring new tools and methods based on 13C-isotopomer analysis and tandem mass spectrometry. This project will 1) develop a new method of dynamic metabolic flux analysis, 2) provide improved techniques for validating metabolic network models, and 3) define optimized growth conditions for T. thermophilus. Broader Impacts: This project promises a major step forward in metabolic network analysis that will be broadly applicable to many organisms of biotechnological and biomedical importance. In addition, this project provides unique opportunities for graduate and undergraduate student education and training in an interdisciplinary environment comprising computational and experimental biology, metabolic flux analysis, mass spectrometry and metabolic network modeling.