Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach

► The natural decomposition approach mathematically derives biologically sound common systems principles for two biotechnologically relevant model prokaryotes. ► The B. subtilis TRN also has a diamond-shaped, matryoshka-like, three-layer hierarchy. ► The κ-value was confirmed as the first mathematical criterion to accurately predict global TFs. ► A set of common physiological global responses govern the functional hierarchies governing B. subtilis and E. coli. ► Conserved modular functions and basal cell machinery were identified and biologically assessed.