SCyCode

The Autotrophy-Heterotrophy Switch in Cyanobacteria: Regulation of glycogen metabolism in response to nitrogen availability

01/01/2019 to 31/12/2021

Glycogen is the major carbon-storage compound in cyanobacteria and its metabolism is central for metabolic homeostasis and essential to survive periods of darkness or macronutrient starvation such as nitrogen starvation. Glycogen synthesis and degradation involves a set of paralogous enzymes, whose precise functional difference is up to now unclear. Phenotypic analyses of mutants indicate a strict functional divergence of the isoenzymes. Moreover, the accumulation and mobilization of glycogen appears to be mainly controlled at the post-translational level. When the unicellular cyanobacterium Synechocystis sp. PCC 6803 is deprived for combined nitrogen sources, the cells accumulate large amounts of glycogen but at the same time, induce the expression of genes for glycogen catabolic enzymes while they become chlorotic. When long-term nitrogen-starved Synechocystis cells are allowed to recover from chlorosis by supplying them with nitrate, the cells immediately switch to glycogen degradation and use a specific glycogen mobilization strategy during the resuscitation process.
Within the larger context of the SCyCode research nertwork, we will use in this subproject the nitrogen-dependent response in glycogen metabolism as a clearly defined experimental system to study cellular principles underlying the switch from glyconeogenetic to glycogen-degrading metabolism. The experimental approaches will be conducted in close collaboration with consortium partners. To gain deeper insight in this process, we will first define the proteome of glycogen granules. Using glycogen from various isoenzyme mutants and from cells in different physiological states, we will obtain insights in functional differences and in the dynamics of the glycogen-associated proteome. Second, we aim to identify the key steps in the enzymatic control governing glycogen synthesis or degradation, with a focus on the role of protein-protein interactions and protein phosphorylation. Finally, we address potential channelling of the metabolites from glycogen degradation using metabolic flux analysis, protein correlation profiling and state-of-the-art cell biology methods