**7. Concluding remarks**

Genome-sequence determination techniques are now applied to a vast range of species. In contrast, techniques to engineer genomes, even of bacteria far smaller than those of higher eukaryotes, remain scarce. Recently, two independent laboratories, one of them ours, demonstrated that whole bacterial genomes can be cloned/manipulated (Itaya et al., 2005). This technological breakthrough has dramatically changed various aspects of genome engineering. However, these cutting-edge technologies are not yet widely applied because they remain labor-intensive with respect to their use in genomes and because the cost of producing correct genomes is high. Besides introducing the reader to the cloning of whole bacterial genomes, this chapter aimed at describing multipurpose systems by which DNA can be routinely engineered. Giant guest DNA cloned in the BGM vector will play a significant role in versatile gene/genome delivery systems. The goal of genome engineering is not only the propagation of microbes but also the engineering of cells addressed by different branches of the life sciences. BAC-based cloning in *E. coli* (Shizuya et al., 1992), one of many DNA cloning technologies, has been revisited in efforts to develop essential cutting-edge tools that can be applied in the BAC-BGM system. The first BAC transfer toand manipulation in the BGM system was achieved as little as 10 years earlier (Itaya et al., 2000). Subsequent publications demonstrated that once the BAC guest was incorporated into the BGM host, modified guest DNA and the novel homologous recombination activity of *B. subtilis* made this possible due to the amazing structural stability of guest DNA. Furthermore, depending on experimental requirements, the structure of recovered fragments can be circular or linear. Emerging genome synthesis technologies will yield giant DNA equivalent to the size of bacterial genomes (Gibson et al., 2008, 2010; Gibson, 2011). We are entering a new era of novel synthetic biology that relies on the synthesis/construction of designed biomaterials. With the aid of newly designed genes and proteins, *de novo* synthetic pathways can be expected to produce yet unknown substances and with the aid of giant DNA, many genes can be delivered simultaneously.

While genome synthesis is gradually changing the way of thinking of researchers in the life sciences, the introduction, maintenance, and manipulation of DNA fragments in BACs will continue to shed light on other host- and biological systems. The *de novo* synthesis of sufficiently large DNA in BACs is only a matter of time and it remains to be seen whether current gene engineering systems will continue to be relevant. We will continue to dedicate our careers to working with DNA pieces irrespective of their size and to shedding light on their divergent applicability to biological systems used in research.
