Reduction-to-synthesis: the dominant approach to genome-scale synthetic biology.

Top-down and bottom-up genome streamlining (or synthesis) are the two distinct modalities for synthetic genome construction. Adaptive laboratory evolution (ALE) plays multiple roles, including debugging system abnormalities, exploring emergent properties of minimal genomes, and providing design principles for genome-scale engineering. The genome 'reductionist' approach is an engineering method that markedly improves strain performance. Advances in genome synthesis technology have opened up new possibilities for the chemical synthesis of customized designer genomes with specialized functions. The synthetic minimal genome JCVI-syn3.0 and its derivatives serve as conducive platforms for studying fundamental aspects of genome composition and organization. Advances in systems and synthetic biology have propelled the construction of reduced bacterial genomes. Genome reduction was initially focused on exploring properties of minimal genomes, but more recently it has been deployed as an engineering strategy to enhance strain performance. This review provides the latest updates on reduced genomes, focusing on dual-track approaches of top-down reduction and bottom-up synthesis for their construction. Using cases from studies that are based on established industrial workhorse strains, we discuss the construction of a series of synthetic phenotypes that are candidates for biotechnological applications. Finally, we address the possible uses of reduced genomes for biotechnological applications and the needed future research directions that may ultimately lead to the total synthesis of rationally designed genomes. [ABSTRACT FROM AUTHOR]