Evaluating Genetic Engineering Trade-offs Through Whole-cell Modeling of Escherichia coli

Riley Juenemann

Stanford University

"Evaluating Genetic Engineering Trade-offs Through Whole-cell Modeling of Escherichia coli"

Genetically engineered bacteria are increasingly utilized to manufacture products that are difficult, expensive, or impractical to synthesize chemically. These products have potential applications ranging from medicine to sustainability. However, metabolic pathway introduction, extensive feedback mechanisms in the cell, and evolutionary forces complicate the engineering of bacterial strains that are well-suited for the task. We need tools that will enable us to anticipate these challenges, as well as increase efficiency and enable novel design. A recently published large-scale model of Escherichia coli has enabled us to simulate many distinct cellular processes and capture their complex interactions on a system-wide level. This model incorporates decades of heterogeneous data collection from E. coli literature to fit over 19,000 parameters for the mechanistic ordinary differential equations describing processes in the cell. We now introduce components related to genetic engineering, with an initial focus on chromosome modification. In this poster, we describe preliminary work analyzing the trade-offs between maximizing exogenous protein production and preserving cell health. Our numerical experiments varying the expression level of a single gfp gene reveal how exogenous gene products sequester resources in key cellular processes. We anticipate that these methods will set the stage for large-scale computational genetic engineering design tools as they develop and expand.

Note: this minisymposia has been accepted, but the abstracts have not yet been finalized.

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