Whole Genome-Scale Metabolic Model of Streptomyces Coelicolor

70441 To analyze, interpret, and predict the function of biological systems, innovative approaches are needed to utilize the information generated from genome research in an integrated fashion. This project will develop novel engineering approaches for studying the systemic capabilities of metabolism in completely sequenced bacterial genomes. In particular, the approach will focus on the development and implementation of a genome-scale metabolic model of Streptomyces coelicolor. Using a constraints-based modeling approach, a metabolic model S. coelicolor will be developed and implemented in an interactive process that begins with the construction of the model from genomic, biochemical, and physiological information. The model will be then utilized to perform integrated modeling/experimental research, capitalizing on high throughput experimental technologies such as array-based transcriptional profiling, proteomics, and metabolite profiling. Phase I will construct the first version model of S. coelicolor, based in large part on the recently sequenced genome of this organism. The model will be refined and validated against existing experimental data on the organism. Commercial applications of the model, along with its utility in interpreting gene expression datasets, will be examined. Commercial Applications and Other Benefits as described by the awardee: A metabolic model of S. coelicolos should have immediate and direct commercial applications in metabolic engineering of industrial strains used to generate novel therapeutic polyketides. The model also has a general commercial value as a tool for guiding genomics research on this organism, and for uses in comparative genomics studies on other organisms for which similar metabolic models have been developed.