Catabolite repression by glucose 6‐phosphate, gluconate and lactose in Escherichia coli

Abstract

SummaryWhile catabolite repression by glucose has been studied extensively and is understood in large detail in Enterobacteriaceae, catabolite repression by carbohydrates that are not transported by the phosphotransferase system (PTS) has always remained an enigma. Examples of non-PTS carbohydrates that cause catabolite repression in Escherichia coli are gluconate, lactose and glucose 6-phosphate. In this article it is shown that enzyme IIA Glc of the PTS is not involved in catabolite repression by these carbon sources. Carbon sources that caused strong catabolite repression of ␤-galactosidase lowered the concentration of both cAMP and the cAMP receptor protein (CRP). A strong correlation was found between the amounts of cAMP and CRP and the strength of the repression. The levels of cAMP and CRP were modulated in various ways. Neither overproduction of CRP nor an increased cAMP concentration could completely relieve the repression by glucose 6-phosphate, lactose and gluconate. Simultaneously increasing the cAMP and the CRP levels was lethal for the cells. In a mutant expressing a constant amount of cAMP-independent CRP* protein, catabolite repression was absent. The same was found in a mutant in which lac transcription is independent of cAMP/CRP. These results, combined with the fact that both the cAMP and the CRP levels are lowered by glucose 6-phosphate, lactose and gluconate, lead to the conclusion that the decreased cAMP and CRP levels are the cause of catabolite repression by these non-PTS carbon sources.

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

“…In this scheme, transport and phosphorylation of glucose or other PTS carbohydrates decrease the extent of phosphorylation of the PTS proteins, including EIIA Glc , and thus lower the activity of adenylate cyclase, whereas growth on non-PTS carbohydrates, particularly poor carbon sources like lactate and succinate, results in fully phosphorylated PTS proteins and the activation of adenylate cyclase. However, this model does not explain how growth on non-PTS carbon sources such as glucose-6-phosphate or gluconate can lead to intracellular cAMP levels similar to, or sometimes lower than, those observed in glucose-grown cells (212,337). Moreover, the inhibitory effect of glucose-6-phosphate is found only in intact but not in toluenized cells (318), and we will discuss this important point later.…”

“…To determine the effect of Crp/cAMP on the expression of catabolic genes without the interference of inducer exclusion, lacZ expression was studied in the presence of the nonmetabolizable inducer IPTG (337), and mal operon expression was studied in the absence of its inducing sugar (210,211). Lactose, gluconate, and glucose-6-P exert strong CCR on lacZ expression, even in a crr mutant, and a clear correlation between cAMP/Crp levels and lacZ expression was observed (337).…”

Signal integration in the galactose network of Escherichia coli

“…However, D-galactose can ultimately be converted to glucose 6-phosphate by the enzymes of the Leloir pathway. Glucose 6-phosphate can inhibit galactose transport (inducer exclusion) (Hogema et al, 1998) and can also reduce the rate of galP transcription by decreasing cAMP levels (Hogema et al, 1997). Transcription of the mglBAC operon is regulated in a similar way, except that it is only partially repressed by GalR.…”

Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

“…coli prefers glucose rather than other sugars for its growth and glucose represses the catabolism of other sugars (Hogema et al, 1997). The glucose PTS is related to catabolite repression, chemotaxis regulation, glycogen phosphorylase, and multiple regulatory interactions (Lux et al, 1995;Postma et al, 1996;Seok et al, 1997;Saier, 1998;Eppler et al, 2002).…”