The inner logic of the TOL regulatory network. (a) Layout of a canonical type I coherent Feed Forward Loop (FFL). In such a motif, a master regulator × activates expression of a target Z both directly and indirectly. Indirect regulation takes through activation of a second transcriptional factor Y which in turn has Z as a target as well. SX and SY are the signals which trigger the activity of × and Y, respectively. The ara operon is shown as an example of this type of FFL, as its expression depends on the interplay between the CRP and AraC regulators, cAMP and arabinose being the SX and SY inducers respectively. (b) Metabolic Amplifier Motif (MAM) found in the TOL network. Compared to the type-I FFL motif, the indirect regulation of Z through the X→Y node remains, but the direct interaction X→Y makes a detour that involves a metabolic (rather than regulatory) action. Specifically, the master regulator × now activates the production of an enzyme (or a metabolic pathway) W, which converts the signal SX into SY. In the TOL system, × and Y are represented by XylR and XylS, while m-xylene (SX) is converted to 3 MBz (SY) by the action of the upper pathway.