Francis Crick first called for a coordinated worldwide scientific effort to determine a “complete solution” of the bacterium Escherichia coli. We have been working for some years now to complete a model of E. coli that takes into account all of the known functions of every well-annotated gene, in order to better understand and predict the behavior of this scientifically-relevant and industrially-significant model organism. Now that a majority of the annotated gene functions have been added to the model, our simulations have generated biological insights that change our perspectives about cellular biology and physiology. As examples, I will present our new findings regarding how metals are utilized in E. coli, as well as the effect of gene organization into operons, and the impact of engineering new gene content into the chromosome.