Genetically engineered bacteria are utilized to produce compounds that are difficult, expensive, or impractical to synthesize chemically. These compounds 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. We now introduce components related to genetic engineering, with an initial focus on chromosome modification. In this presentation, I will give an overview of whole-cell modeling and describe preliminary work analyzing the trade-offs between maximizing compound production and preserving cell health. Our numerical experiments varying the expression level of a single gfp gene reveal how exogenous gene overexpression burdens cellular production machinery. We anticipate that these methods will set the stage for large-scale computational genetic engineering design tools as they develop and expand.