We now turn our attention to examining how the genome-scale reconstruction process for metabolic networks has been applied to particular organisms. The reconstruction process is enabled by genome sequencing. The first full genomic sequence appeared for Haemophilus influenzae in 1995. Four years later, the genome-scale metabolic reconstruction for H. influenzae appeared, the first of its kind [105]. The second genome-scale reconstruction to appear was for E. coli K-12 MG1655 in 2000 [106]. Due to a wealth of bibliomic data available for E. coli, there have been several subsequent updates and expansions of this reconstruction. This chapter discusses the history of the reconstruction of the genome-scale metabolic network in E. coli. We then discuss how this network reconstruction can be converted to a computational model and illustrate the range of basic scientific questions that can be addressed and describe its practical uses.

Some Basic Facts about E. coli

E. coli is a Gram-negative bacterium, a prokaryote belonging to the Enterobacteria family. It is perhaps the best-characterized organism as evidenced by its high Species Knowledge Index (SKI) [184, 295]. Non-pathogenic strains have proven to be the workhorse of the biotechnology industry. E. coli is normally harmless, but needs only to acquire a combination of a few mobile genetic elements to become a highly adapted pathogen [92]. Pathogenic strains cause a range of diseases, from gastroenteritis to extra-intestinal infections of the urinary tract, bloodstream, and central nervous system (see Figure 4.1). The worldwide burden of these diseases is high. With the low cost of sequencing, there are now many strains of E. coli that have been sequenced [251].

E. coli is a remarkable and diverse organism. It can grow on a wide variety of different carbon and nitrogen sources both aerobically and anaerobically. Fundamentally, its life cycle consists of five key shifts in growth conditions: a heat shock (i.e., from ambient temperature to 37°C), a pH shock (from neutral to gastric pH of about 2), oxygen deprivation, nutritional richness and community competition, and finally a cold shock back to ambient temperature.