Extended Data Figure 7. Growth on glycerol, xylose or fucose with various second substrates.
a. This diagram illustrates the difference in the effect of glycolytic and gluconeogenic substrates on glycerol uptake. The uptake and catabolism of glycerol, gluconeogenic substrates and glycolytic substrates are drawn as three pathways (gray arrows) that merge at different places. In the regulation (red lines), two flux-sensors are involved: one (FBP) senses the upper-glycolytic flux jL, the other (cAMP-Crp) the total carbon flux jtot. Crucially, both flux sensors are required to fully suppress glycerol uptake; this is symbolized in the diagram using the symbol of a logical AND gate. Glycolytic substrates contribute both to the upper-glycolytic flux and the total carbon flux. A sufficiently large glycolytic flux therefore activates both the upper-glycolytic flux sensor AND the total-flux sensor, which together suppress glycerol uptake. In contrast, gluconeogenic substrates do not contribute to the upper-glycolytic flux and will not fully inhibit glycerol uptake even if they provide a large carbon flux. (Through the total-flux sensor cAMP-Crp, gluconeogenic substrates will affect glycerol uptake mildly, but both substrates remain co-utilized.) This difference between glycolytic and gluconeogenic substrates underlies the pattern in Fig. 5c.
b. A pattern similar to Fig. 5c is obtained if glycerol is replaced by xylose. Shown here is the growth rate of WT cells (NCM3722) in M9 medium24 on xylose plus a second substrate plotted against growth rate with the second substrate only, for a variety of “second” substrates. The growth rate on xylose only is indicated by horizontal and vertical dotted lines. The growth rate on both substrates shows a similar dependence on the “second” substrate species as seen in Fig. 5c of the main text: If the second carbon substrate is processed at least partially by upper glycolysis (blue circles) the growth rate is approximately the larger of the two single-substrate growth rates, possibly with an exception for mannose. If on the other hand the second substrate is a gluconeogenic substrate (orange circles) the growth rate on both substrates is usually larger than either of the two single-substrate growth rates.
c. Same as Panel b, but for fucose as the “first” substrate.