Escherichia coli adenylate cyclase homepage

The transport of PTS-sugars other than glucose can affect the phosphorylation of Enzyme IIA^glc simply by generating competition for phosphorylation between the phosphotransfer proteins.  Such competition indirectly regulates adenylate cyclase activity.

This type of regulation has been proposed by M. Crasnier-Mednansky and coworkers in 1997 [Microbiology].  It occurs when enhanced transport of the PTS-sugar fructose takes place.

The sequential transfer of phosphate from PEP to fructose does not involve, unlike other PTS, HPr but the diphosphoryl transfer protein, FruB [Medline].

In fruR mutant strains lacking the fructose repressor FruR (also called Cra), Enzyme IIA^glc is largely unphosphorylated when cells are grown in fructose-containing medium because FruA and FruB are over-expressed thus leading to competition for phosphorylation between FruB and HPr.

Because of the competition between the phosphoproteins, leading to an unphosphorylated state for Enzyme IIA^glc, adenylate cyclase becomes "inactive" (in idle mode).  Therefore fruR mutant strains grown on fructose exhibit cAMP levels that are much lower than those in wild-type strains grown on fructose.  With carbon sources other than fructose, cAMP levels of fruR and wild-type strains are comparable [Microbiology]¹.  One of the physiological consequences of Enzyme IIA^glc unphosphorylation is that fructose can substitute for glucose in producing diauxie, but only in fruR strains [MIeJ].

Competition for phosphorylation between PTS constituents seems to be a crucial determinant of adenylate cyclase regulation, as exemplified by the study of fruR mutant strains.

Competition for phosphorylation is also likely to occur when transport of several PTS-sugars takes place.  Limited phosphoryl flux may be a constituent of the winner-take-all behavior, as revealed by theoretical studies of metabolic switching in the PTS [Biophysical Journal].

In the case of a non-PTS carbon source, for example glucose-6-phosphate, the regulation of adenylate cyclase activity is more difficult to apprehend, as glucose-6-phosphate transport or metabolism is not known to involve PTS proteins, especially Enzyme IIA^glc.

Footnote:

¹ In the 2007 JB article "Analysis of the correlation between growth rates, EIIA^Crr phosphorylation and intracellular cAMP levels in Escherichia coli K-12" by K. Bettenbrock and coworkers it was improperly reported, by referring to the 1997 Microbiology article, that lack of HPr enhances cAMP production in fructose-grown E. coli.  Generally lack of HPr results in a low production of cAMP!