Metabolic Engineering of Aerobic Glucose Catabolism in Escherichia Coli

该项目旨在为大肠杆菌中心碳代谢的重大基因重组提供一个重要的框架，以增加有价值的产物的合成。该项目还计划在研究细胞对环境或遗传操作的反应时，为新的通用监测和分析方法做出贡献。该项目的具体总体目标是通过对碳流进行基因改造来减少大肠杆菌有氧生长过程中醋酸盐的形成。这是通过以下方式完成的：-确定可将碳流引向醋酸盐的代谢信号。-确定与在遗传水平上对触发醋酸盐产生的环境的反应有关的蛋白质。-评估导致产生醋酸盐的条件下的总体葡萄糖消耗、生长和醋酸盐形成动力学和化学计量。-详细描述几种现有的基因结构，这些结构具有或可能显示出改变的醋酸盐生产代谢。-确定和绘制新的基因改变，以促进醋酸盐生产环境中的生长。

This project intends to provide an important framework for major genetic restructuring of central carbon metabolism in E. coli for the purpose of increasing synthesis of valuable products. This project also plans to contribute to new monitoring and analysis methods of general utility in studying cell response to environmental or genetic manipulation. The specific overall objective of this project is to reduce acetate formation during aerobic growth of E. coli by genetic modification of carbon flow. This is to be done by: - Identifying metabolic signals which are candidates for directing carbon flow towards acetate. - Identifying proteins associated with responses at the genetic level to environments which trigger acetate production. - Evaluating overall glucose consumption, growth and acetate formation kinetics and stoichiometry under conditions which result in acetate production. - Characterizing in detail several existing genetic constructs which possess or which are likely to exhibit altered acetate production metabolism. - Identifying and mapping new genetic alterations which enhance growth in acetate-producing environments.