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Understanding cellular life requires a comprehensive knowledge of the essential functions and components of a cell as well as of their interactions. Minimized genomes are an important tool toward gaining this knowledge. In this issue, genome-reduced strains of the model bacterium Bacillus subtilis are described and deletions affecting the transcription regulatory network of the cell, translation resource allocation, and metabolism are described. The results suggest approaches to further genome reduction toward the final aim of a minimal cell in which all functions are understood. The illustration shows the deleted genomic regions (indicated by bars) in four viable genome-reduced B. subtilis strains. The word cloud surrounding the genome map provides important key words relevant for the study. (Cover illustration by Fabian M. Commichau. [For details, see Reuß et al., pp. 289–299.])

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