The objective of this project is to investigate a cybernetic model-based approach to metabolic engineering. This approach would address various ways in which the metabolic engineering goal may be compromised by regulatory phenomena in the overall pathway and to provide for the optimal design of genetic changes. The formulation of the cybernetic model, based on experimental data with both wild type cells and selected genetic strains derived therefrom, is viewed to capture the regulatory features in the entire pathway. Such a model forms the basis of examining the consequences of all possible genetic changes in the pathway. Also, the resulting model is suited for model-based optimal control of the bioreactor for maximizing product formation. The model system is an E. coli strain that produces ethanol. This collaborative GOALI project involves Purdue University, the University of Delaware, and the DuPont Chemical Company.