Efforts to Minimise the Bacterial Genome as a Free-Living Growing System

SIMPLE SUMMARY: Genome reduction is a top-down approach to achieve the minimal genetic information essential for a living cell. The most popular and well-studied cell model for genome reduction was performed with Escherichia coli, advantageous for its rapid growth and easy manipulation. This mini-review discusses genome-reduced Escherichia coli by paying particular attention to growth fitness, the fundamental property of life. It recapitulates the efforts to minimise Escherichia coli genomes, focusing on experimental and computational achievements in the systematic understanding of being alive. ABSTRACT: Exploring the minimal genetic requirements for cells to maintain free living is an exciting topic in biology. Multiple approaches are employed to address the question of the minimal genome. In addition to constructing the synthetic genome in the test tube, reducing the size of the wild-type genome is a practical approach for obtaining the essential genomic sequence for living cells. The well-studied Escherichia coli has been used as a model organism for genome reduction owing to its fast growth and easy manipulation. Extensive studies have reported how to reduce the bacterial genome and the collections of genomic disturbed strains acquired, which were sufficiently reviewed previously. However, the common issue of growth decrease caused by genetic disturbance remains largely unaddressed. This mini-review discusses the considerable efforts made to improve growth fitness, which was decreased due to genome reduction. The proposal and perspective are clarified for further accumulated genetic deletion to minimise the Escherichia coli genome in terms of genome reduction, experimental evolution, medium optimization, and machine learning.