Expanding the knowledge on the role of protein phosphorylation in the regulation of carbon metabolism

01/01/2025 to 31/12/2027

The regulation of glycogen metabolism is crucial for the survival of a variety of organisms. Fine-tuning of the
activity of the enzymes involved in glycogen synthesis and degradation is essential to ensure the ability to
accumulate or degrade glycogen according to cellular requirements. This fine regulation of enzyme activity is
often achieved by protein phosphorylation. Our preliminary work has identified phosphoglucomutases 1 and 2
(PGM1 and PGM2) as key enzymes in the regulation of glycogen metabolism in the unicellular cyanobacterium
Synechocystis sp. PCC 6803, and phosphorylation of these proteins as an essential regulatory mechanism.
PGM1 catalyzes a central reaction in carbon metabolism (the conversion between glucose-1-phosphate and
glucose-6-phosphate) and is required for glycogen synthesis and glycogen degradation. PGM2 produces a
substance, glucose-1,6-bisphosphate, which is an activator of PGM1. Glucose-1,6-bisphosphate phosphorylates
PGM1 in its catalytic center (Ser 152) and activates the enzyme, enabling glycogen synthesis and glycogen
degradation. A second phosphorylation site in PGM1 (Ser 47) inhibits its activity when it is not required.
These regulatory mechanisms appear to be conserved from bacteria to humans. However, some aspects of
these regulatory processes remain unclear. This project aims to address two main questions: i)
which other enzymes are phosphorylated by glucose-1,6-bisphosphate and ii) how Ser 47 is phosphorylated.