Award For Creativity in Engineering for Kimberlee Wallace

次生代谢物是由细胞产生但不是细胞生长所必需的化合物。商业上重要的次生代谢物包括抗生素、色素和香料。由于对产生这些化合物的复杂途径的了解有限，提高生产率的传统方法涉及经验技术。在早期，这些实证策略导致生产率呈指数增长；然而，目前这些技术不太成功，导致每年的生产力增长只有几个百分点。为了获得更大的生产力改进，必须根据生物合成的细胞内速率限制知识开发合理的技术。本研究的目的是检查细胞内环境并确定次级代谢物产生的速率限制。研究者建议从三个层面来审视监管。首先，一种关键途径酶的水平将被量化，以确定酶的可用性是否限制了生物合成。其次，将检查前体供应，以确定代谢物通过该途径的通量是否限制了生产。第三，将检查反应终产物对生物合成的影响，以确定细胞内水平是否抑制生产。

Secondary metabolites are compounds which are produced by the cell but are not required for the growth of the cell. Examples of commercially important secondary metabolites include the antibiotics, pigments, and fragrances. Due to the limited knowledge of the complex pathways from which these compounds are produced, traditional methods for improving productivity have involved empirical techniques. In early years, these empirical strategies resulted in exponential productivity increases; however, currently these techniques are less successful, resulting in annual productivity increases of only a few percent. To obtain greater productivity improvements, rational techniques must be developed based upon knowledge of intracellular rate limitations to biosynthesis. %%% The purpose of this study is to examine the intracellular environment and determine the rate limitation to secondary metabolite production. The investigator proposes to examine regulation at three levels. First, levels of a key pathway enzyme will be quantified to determine if enzyme availability is a limitation to biosynthesis. Second, precursor supplies will be examined to determine if the flux of metabolites through the pathway limits production. Third, the effect of reaction endproducts on biosynthesis will be examined to determine if intracellular levels inhibit production.