Understanding and controlling cellular metabolism is crucial to applications ranging from industrial biosynthesis to bioenergy production, but is significantly hindered by limited information about the dynamics and regulation of metabolism. This CAREER project aims to use a computationally-driven approach to engineering cells to produce valuable chemicals, to be derived from cell-wide measurements of metabolite levels within the cell. To achieve this, a new metabolic model that includes regulation will be developed and used in an iterative experimental/computational manner for optimizing production of the valuable chemical succinic acid in the yeasts Saccharomyces cerevisiae and S. mikatae. This work will be the first of its kind to directly use cell-wide measurements of metabolites to drive metabolic engineering. Its successful completion will support the refocusing on rational design in metabolic engineering, and also increase the scope of chemicals that could be produced biosynthetically.
Broader Impact This project has the potential to enable more efficient and effective engineering of metabolism, with applications ranging from the low-cost production of useful chemicals that become affordable to developing countries, impacting the quality of life for millions of people, to the facilitation of economically feasible production of biofuels for sustainable energy. Additionally, models that will be constructed for multiple species could help elucidate mechanisms of metabolic evolution. The integrated research and education plan of this project seeks to foster quantitative, whole system-level thinking in children, and to encourage the participation of underrepresented groups in engineering. To do so, existing educational programs that promote this mindset will be implemented in local socioeconomically-disadvantaged and predominantly minority schools. Also, a synthetic biology team will be assembled at a local high school to stimulate interest in systems biology, synthetic biology, and bioengineering, with targeted recruitment of females (underrepresented in engineering).
