Biology subjects

Neumann, N.

Publications and source records attributed to Neumann, N..

3 recordsLinked to original sources

bioRxiv2022

On the role and regulation of glycogen catabolic isoenzymes in Synechocystis sp. PCC6803

Glycogen serves as the main carbon storage polymer in many organisms and is widespread across all domains of life. In cyanobacteria, glycogen degradation is crucial for metabolic transitions during dark phases or during resuscitation from nitrogen starvation. Like many other cyanobacteria, Synechocystis sp. PCC 6803 possesses multiple homologues of glycogen catabolizing enzymes, though their specific roles and regulatory mechanisms are only partially understood. Here we demonstrate through biochemical analysis that the glycogen phosphorylase GlgP1, known to promote high temperature acclimation, is uniquely regulated by a C-terminal redox switch found certain cyanobacteria. This is the first evidence of redox regulation of a prokaryotic glycogen degrading enzyme. Notably, GlgP1 is activated via oxidation by reactive oxygen species and inactivated by reducing agents, with thioredoxin being the most effective inhibitor tested. The physiological implications of this redox regulation are discussed. Additionally, a biochemically characterization of the two glycogen debranching isoenzymes GlgX1 and GlgX2 revealed that only GlgX1 exhibits debranching activity, while GlgX2 does not. Mutant analysis confirmed that GlgX1 plays an essential role in glycogen mobilization, being crucial for resuscitation from chlorosis and survival during extended dark periods. In contrast the physiological function of GlgX2 remains unclear.

microbiology↗

bioRxiv2021

Glucose-1,6-bisphosphate, a key metabolic regulator, is synthesized by a distinct family of α-D-phosphohexomutases widely distributed in prokaryotes

The reactions of -D-phosphohexomutases (PHM) are ubiquitous, key to primary metabolism and essential for several processes in all domains of life. The functionality of these enzymes relies on an initial auto-phosphorylation step which requires the presence of -D-glucose-1,6-bisphosphate (Glc-1,6-BP). While well investigated in vertebrates, the origin of this activator compound in bacteria is unknown. Here we show that the Slr1334 protein from the unicellular cyanobacterium Synechocysitis sp. PCC 6803 is a Glc-1,6-BP-synthase. Biochemical analysis revealed that Slr1334 efficiently converts fructose-1,6-bisphosphate (Frc-1,6-BP) and -D-glucose-1-phosphate/-D-glucose-6-phosphate into Glc-1,6-BP and also catalyzes the reverse reaction. As inferred from phylogenetic analysis, the slr1334 product belongs to a primordial subfamily of PHMs that is present especially in deeply branching bacteria and also includes human commensals and pathogens. Remarkably, the homologue of Slr1334 in the human gut bacterium Bacteroides salyersiae catalyzes the same reaction, suggesting a conserved and essential role for the members of this PHM subfamily.

microbiology↗

bioRxiv2021

Regulatory phosphorylation site tunes Phosphoglucomutase 1 as a metabolic valve to control mobilization of glycogen stores.

Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated at a peripheral residue (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans. Significance statementIn this study, we identified phosphoglucomutase 1 (PGM1) as a central metabolic valve that regulates the utilization of the glycogen reserves. We showed that post-translational modification of PGM1 via phosphorylation at a peripheral residue is a key, evolutionary-conserved regulatory mechanism that controls PGM1 activity and the mobilization of the glycogen stores.

microbiology↗