The fructose repressor

In Escherichia coli, fructose is transported and phosphorylated to fructose-1-phosphate in a reaction involving the phosphotransferase system (PTS).  Expression of the fructose operon (fruBKA) encoding FruB (the diphosphoryl transfer protein), FruK (fructose-1-phosphate kinase) and FruA (the fructose permease renamed Enzyme IIB'BCFru) is negatively controlled by a transcription factor originally called the fructose repressor or FruR, FruR at UniProtKB.

It was proposed that FruR should be renamed Cra for Catabolite repressor/activator protein.  This proposal was based upon the discovery that (i) FruR was a pleiotropic regulator controlling synthesis of enzymes involved in carbon metabolism and (ii) several catabolites were controlling the transcriptional regulation by FruR (Saier MH Jr, 1996).

However, the negative transcriptional regulation exerted by FruR on the glucose PTS genes (Ryu S, 1995) does not seem to be physiologically relevant, as indicated by measurements of glucose uptake rates in glucose-grown fruR mutant strains (Perrenoud A, 2005).  Also, the repressive effect of FruR on transcription of the pykF gene encoding pyruvate kinase (Bledig SA, 1996) and pfkA encoding phosphofructokinase (Chin AM, 1989), and subsequent effects on the Embden-Meyerhof-Parnas (EMB) pathway, were not confirmed (Perrenoud A, 2005).

As regards the control of FruR by different catabolites, data indicated transcriptional regulation by FruR is mainly dependent on the presence of intracellular fructose-1-phosphate.  Indeed it has not been established that catabolites other than fructose-1-phosphate can act on FruR in vivoIn vitro, transcriptional regulation by FruR was not affected by catabolites other than fructose-1-phosphate and much less effectively fructose-1, 6-bisphosphate (Ramseier TM, 1993).  Micromolar concentrations of fructose-1-phosphate as opposed to millimolar concentrations of fructose-1, 6-bisphosphate displaced FruR from operator sites of FruR-dependent genes (Ramseier TM, 1996).  It is to be noted that the concentration of fructose-1, 6 bisphosphate was reported to be in the micromolar range with a carbon source such as acetate.  The proposal by Kochanowski K, 2013 the activity of FruR is regulated 'via fructose-1, 6 bisphosphate in a flux-dependent manner', as originally predicted by Kotte O, 2010, is questionable (Comment).  In Pseudomonas putida, fructose-1-phosphate is the only physiological effector of FruR however the reported in vitro effect of fructose-1, 6-bisphosphate on E. coli FruR was not definitely ruled out (Chavarria M, 2014).

Finally, the FruR-mediated regulation of adenylate cyclase depends on the rapid uptake of fructose and is observed only in fructose-grown cells (Crasnier-Mednansky M, 1997).

Chapter III