A New Piece of an Old Jigsaw: Glucose Kinase Is Activated Posttranslationally in a Glucose Transport-Dependent Manner in <i>Streptomyces coelicolor </i>A3(2)

Abstract

Members of the soil-dwelling prokaryotic genus Streptomyces are indispensable for the recycling of complex polysaccharides, and produce a wide range of natural products. Nutrient limitation is likely to be a major signal for the onset of their development, resulting in spore formation by specialized aerial hyphae. Streptomycetes grow on numerous carbon sources, which they utilize in a preferential manner. The main signaling pathway underlying this phenomenon is carbon catabolite repression, which in streptomycetes is totally dependent on the glycolytic enzyme glucose kinase (Glk). How Glk exerts this fascinating dual role (metabolic and regulatory) is still largely a mystery. We show here that while Glk is made constitutively throughout the growth of Streptomyces coelicolor A3(2), its catalytic activity is modulated in a carbon source-dependent manner: while cultures growing exponentially on glucose exhibit high Glk activity, mannitol- grown cultures show negligible activity. Glk activity was directly proportional to the amount of two Glk isoforms observed by Western blot analysis. The activity profile of GlcP, the major glucose permease, correlated very well with that of Glk. Our data are consistent with a direct interaction between Glk and GlcP, suggesting that a Glk-GlcP permease complex is required for efficient glucose transport by metabolic trapping. This is supported by the strongly reduced accumulation of glucose in glucose kinase mutants. A model to explain our data is presented.

The enigmatic lack of glucose utilization in Streptomyces clavuligerus is due to inefficient expression of the glucose permease gene

“…Proteins GlkA and GlcP have been proposed to form an active complex, GlkA-GlcP, to internalize and phosphorylate glucose (van Wezel et al, 2007). Our results support this proposal.…”

“…S. coelicolor glucose kinase formation is constitutive, but its activation is mediated by a glucose-dependent posttranslational modification (van Wezel et al, 2007). S. clavuligerus contains a constitutively expressed glkA gene, and shows glucose kinase activity 25 % lower than the activity found in S. coelicolor.…”

Carbon source regulation of antibiotic production

“…123 However, a direct effect of SCO2127 on the activation of Glk or GlcP cannot be discarded. In this regard, the apparent binding of Glk to the major glucose transport system of S. coelicolor (GlcP) reported by van Wezel et al 134 might be mediated by SCO2127, increasing the efficiency of glucose metabolism.…”

“…133 However, these attempts did not allow identification of a GlkA-interacting protein making interaction between Glk and these transcriptional regulators unlikely. On the other hand, apparent binding between Glk and the glucose transporter GlcP has been reported, 134 suggesting that a Glk-GlcP complex is required for efficient glucose metabolism.…”

Characterization of Polyphosphate Glucokinase SCO5059 fromStreptomyces coelicolorA3(2)

“…They are industrially important as producers of antibiotics, antitumor agents, immune-suppressants, and insecticides. For these reasons, the regulation of glk gene expression, [2][3][4][5][6][7][8][9] and the biochemistry studies of Streptomycete Glks, have been extensively investigated.…”