From Springer Nature via Jisc Publications RouterHistory: received 2021-03-24, accepted 2021-10-06, registration 2021-10-12, pub-electronic 2021-10-29, online 2021-10-29, collection 2021-12Publication status: PublishedFunder: Commonwealth Scholarship Commission (CSC); doi: https://doi.org/10.13039/501100000867; Grant(s): INCN-2018-57Funder: RCUK | Engineering and Physical Sciences Research Council (EPSRC); doi: https://doi.org/10.13039/501100000266; Grant(s): EP/M013219/1, EP/023755/1Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/M011208/1, BB/M011208/1, BB/P01738X/1Abstract: Biological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions