Development of a Mechanistic Model for Sugar-Utilization Regulatory Systems

Jiangfeng Zhu1, Ryan Peacock2, Jacqueline V. Shanks3, Ramon Gonzalez4, and Ka-Yiu San1. (1) Department of Bioengineering, Rice University, Houston, TX 77005, (2) Rice University, Bioengineering Department, 6100 Main Street, Houston, TX 77005, (3) Iowa State University, Dept. of Chemical and Biological Engineering, 3031 Sweeney Hall, Iowa State University, Ames, IA 50011, (4) Chemical and Biomolecular Engineering, Rice University, MS-362, P.O. Box 1892, Houston, TX 77251-1892

Lignocellulosic biomass such as agricultural and wood residues, crops, and byproduct streams provides a low cost and uniquely sustainable resource for producing many fuels and chemicals. The microbial transformation of its constituent sugars (5-and 6-carbon sugars) into commodity chemicals is one of the most important steps in this process. The process requires an organism, such as metabolic engineered E. coli, that is capable of fermenting sugar mixtures containing 5- and 6-carbon sugars. E. coli possesses well developed sugar utilization and regulatory systems (SURS), which senses the presence of preferential carbon source such as glucose in the culture media and induce or represses the expression levels of some genes to control the utilization of different sugars. Our laboratories have been involved in developing a modeling framework to integrate genomic information in the overall metabolic flux analysis scheme. The concept is very powerful as it is one of the very few attempts to render static databases into one that is dynamic. That is, the proposed framework should allow one to capture the cellular behaviors in response to environmental/genetic perturbations. This is in sharp contrast to the traditional FBA analysis that normally starts with predetermined metabolic networks (maps). In this presentation, we will describe our recent progress in the development of such a model for the SURS. Our preliminary model considers the elements such as glucose uptake through PTS, glucose metabolism through glycolysis, and the regulatory molecules that play a significant role in altering xylose utilization.