Genomic engineering is the synthetic assembly of complete chromosomal DNA that is more or less derived from natural genomic sequences. Genomic engineering is the top-down, global approach to synthetic biology; to be distinguished from bottom-up, local genetic circuit engineering.Artificial simplification of bacterial genomes is thought to have the potential to yield cells with reduced complexity, enhanced genetic stability, and improved cellular economy. Of these goals, economical gains, supposedly due to the elimination of superfluous genetic material, and manifested in elevated growth parameters in selected niches, have not yet been convincingly knowledge achieved. This failure might stem from limitations of the targeted genome reduction approach that assumes full of gene functions and interactions, and allows only a limited number of reduction trajectories to interrogate. To explore the potential fitness benefits of genome reduction, we generated successive random deletions in E. coli by a novel, selection-driven, iterative streamlining process.