Figure 3

Predicted response of the Mycobacerium tuberculosis to slower growth rate induced by carbon limitation. Only selected central metabolic pathways are illustrated. The slower growth rate was simulated by adjusting glycerol uptake rates to obtain a predicted growth rate of 0.03 (fast growth rate corresponding to doubling time of 23 hours) and 0.01 (slow growth rate corresponding to doubling time of 69 hours). Arrows indicate biochemical reactions or pathways, and the number on the arrow indicates the response of the genome-scale metabolic network of M. tuberculosis (GSMN-TB) to slower growth rate. The numbers were calculated by flux variability analysis (FVA) as the ratios of midpoints of flux ranges obtained for slow and fast growth rates. The values have been normalized to account for the lower absolute carbon flux values at the slower growth rate, except for the glycerol uptake rate, which is not normalized to emphasize the fact that the growth rate was reduced by limiting glycerol. The direction of the arrows indicates the direct of flux, not reaction reversibility. CoA, coenzyme A; E4P, D-erythrose-4-phosphate; MK, menaquinone; MKH, menaquinol; S7P, D-sedoheptulose-7-phosphate.