Formalization the TOL network as a logic circuit. (a) Interplay between transcriptional factors. The scheme blows up the divergent Pr/Ps region that controls expression of XylR and XylS, respectively. In the absence of m-xylene, XylR represses weakly its own transcription from Pr, and an inactive form of XylS (XylSi) is expressed through a low-constitutive divergent promoter Ps2. The presence of m-xylene both increases XylR auto-repression and activates the σ54-dependent Ps1 promoter, thereby strengthening XylS expression to the point of reaching a high concentration (XylSh) able to activate the Pm promoter of the lower operon (see text). (b) Basic logic gates (AND, OR and NOT) used for constructing the model presented in this work, along with the respective truth tables. (c) The minimal TOL logicome, which represents the core logic interactions taking place in the system. Expression of the upper pathway is represented by an AND gate having both XylR and m-xylene as inputs, the same being true for XylS production. 3 MBz synthesis is represented also as an AND gate with the upper pathway and m-xylene as the inputs. For expression of meta, the formation of XylSa (XylS plus 3 MBz) is presented as an AND gate where the output is connected to an OR gate, where the second input is overproduced XylS itself (XylSh). This is because Pm can be induced by either low level-XylS along with 3 MBz as an effector or high level, effector-free XylS (see text). Finally, degradation of 3 MBz into TCA metabolic intermediate is represented by an AND gate with the meta enzymes and the 3 MBz substrate as inputs. Note that the XylR auto-repression loop has been eliminated for the model, since the actual levels of this protein are known to change little in the presence/absence of m-xylene.
Silva-Rocha et al. BMC Systems Biology 2011 5:191 doi:10.1186/1752-0509-5-191