“…Phthalate and its isomers are known toxic compounds. ,, Here, we show that phthalate is toxic to both organisms, even when an additional carbon source is present (Supporting Information Figure S4), but that there are a number of adaptations adopted by the two isolates to deal with phthalate toxicity, for example, via conversion into phthalic anhydride, as observed by metabolomics, or the production of stress response mechanisms and efflux pumps, as shown by proteomics. While phthalic anhydride was previously reported in other PAE biodegradation studies ,, and is known to be less toxic than phthalic acid, the mechanisms or reasons for its production were not discussed in these studies. While it is possible that the dehydration of phthalate could occur spontaneously at high temperatures, many previous PAE degradation studies have not reported phthalic anhydride production. ,− Carboxylic acid anhydride production usually requires the presence of a catalyst or an enzyme under the physiological conditions used here and, while we suggest a dihydroxy acid dehydratase as being responsible for phthalic anhydride production, this compound could also be produced by phthaloyl-CoA decay during the anaerobic degradation of phthalate, , although the enzyme responsible for the production of phthaloyl-CoA (i.e., succinyl-CoA/phthalate-CoA transferase) was not found in either isolate (Supporting Information Tables S2, S5, and S6).…”