(143d) Tools for Engineering Non-Growth Metabolism

Tyo, K. E. J., Northwestern University
Greene, J., Northwestern University
Bothfeld, W., Northwestern University
Brotz, M., Northwestern University
Broadbelt, L. J., Northwestern University

Stationary phase metabolism that is not carbon-limited is ideal for metabolic engineering.  Without cell growth, feedstocks can be efficiently converted to product and toxicity that leads to growth-inhibition is irrelevant.  However, to date, most metabolic engineering tools have focused on engineering growing cells, with only modest effort being applied to non-growing cells.  While there is great promise, non-growth metabolic engineering presents new challenges, as post-translational (e.g., allosteric) enzyme regulation dominates control and is not amenable to analysis by transcriptomics/proteomics or engineering by altering promoters.

Our lab is developing a suite of tools to engineer non-growth metabolism in E. coli.  I will discuss computational and experimental efforts to understand, predict, and control non-growth metabolic regulation for optimal biosynthesis.  We are developing non-growth metabolic models that accurately reproduce different non-growth conditions and predict metabolic perturbations.  These models are complemented by experimental strategies to uncover and overcome condition-specific metabolic regulation.  Finally, we are developing next-gen synthetic biology circuits to manage the transition to non-growth and optimize product synthesis.  This work should be applicable to a broad range of products and substantially improve process economics by improving titers, yields, and productivity.

Our strategy of model-driven metabolic engineering is deeply rooted in the training experience and research approach from my time in the Stephanopoulos lab.  It is an honor to be mentored by Greg, and a pleasure to honor his achievements.