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.
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