Plasticity of nutrient quality.

a, We replaced chromosomal promoters of transporters and metabolic enzymes required for mannose metabolism with the promoter of glucose transporter (P-ptsG). To prevent repression due to lack of glucose, we knocked out the glucose-specific transcriptional regulator Mlc. Finally, to ensure that carbon flux from processed mannose enters the glycolysis pathway, we placed mannose-6-phosphate isomerase under a strong constitutive promoter (P-tet). We refer to this strain as the swapped promoter strain (YCE119). (construct map illustration created with Biorender.) b, Growth rates of wildtype and swapped promoter strain (YCE119) on glucose and mannose. Mannose is one of the slowest substrates for the wildtype (orange circles), and glucose is often considered the best substrate of E. coli with the fastest growth rates in minimal medium (blue circles). Yet the swapped promoter strain grows on mannose as fast as the wildtype on glucose (orange triangles). Therefore, the genetic modifications in the swapped promoter strain have changed the nutrient quality of mannose into the nutrient quality of glucose. This means that nutrient quality is not limited by fundamental biochemical constraints. Unpaired t-test was performed, and following P-values were obtained. WT Glucose:WT mannose P-value<0.0001. WT Mannose:YCE 119 Mannose P-value<0.0001, and WT Glucose:YCE119 Mannose: non-significant (ns) c, Data from Towbin et al. [17], who titrated cAMP levels on different substrates. “Good” substrates have a higher peak growth rate at lower levels of cAMP. d, An inverse correlation of endogenous Crp activity on different substrates with growth rate on the respective substrate from Towbin et al. [17]. Poor substrates require higher cAMP levels for maximum growth. A similar relationship is found when plotting CRP activity vs. growth rate for maximum growth rate (S3 Fig).