Figure 1

Overview of the TOL network. At the metabolic level, m-xylene is first converted to 3-methylbenzoate (3 MBz) through the action of the enzymes encoded by the upper operon, and this intermediate compound is further metabolized into the TCA cycle by the activities born by the meta operon. In the sketch, XylR and XylS are transcriptional regulators while Pu, Pm, Ps and Pr are promoters. At the regulatory level, the master regulatory gene xylR is encoded in a location adjacent to the end of the meta operon and expressed from the Pr promoter (not to scale). The corresponding TF is produced in the so-called inactive form (XylRi). This protein changes to an active form (XylRa) when bound to the inducer m-xylene or its first intermediate 3-methylbenzyl alcohol (3 MBA, not shown). XylRa then activates both Pu and Ps, which triggers expression of the upper pathway and stimulates production of XylS respectively [50]. In the absence of m-xylene, this second regulator XylS is produced at low levels, and it changes from the inactive form XylSi to the transcriptionally proficient XylSa by binding to 3 MBz [23]. This XylSa form is able to induce meta pathway expression by activating Pm. But, concomitantly, high levels of XylS triggered by XylRa-mediated Ps activation can also induce Pm activity. This activation loop is formalized as an alternative XylS form (XylSh, for hyper-expressed XylS [32])