| dc.contributor.advisor | Stülke, Jörg Prof. Dr. | |
| dc.contributor.author | Zschiedrich, Christopher Patrick | |
| dc.date.accessioned | 2015-09-22T09:43:03Z | |
| dc.date.available | 2015-09-22T09:43:03Z | |
| dc.date.issued | 2015-09-22 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-9623-4 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5280 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5280 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Nebenwege des zentralen Kohlenstoffmetabolismus von Bacillus subtilis: Regulation der Methylglyoxalsynthase und der Zitratsynthase CitA | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Alternative metabolic pathways of the central carbon metabolism of Bacillus subtilis: Regulation of the methylglyoxal synthase and the citrate synthase CitA | de |
| dc.contributor.referee | Gatz, Christiane Prof. Dr. | |
| dc.date.examination | 2015-10-20 | |
| dc.description.abstracteng | The phosphoenolpyruvate phosphotransferase system plays a crucial role in carbon metabolism of Bacillus subtilis. Besides uptake of different sugars the components of the PTS exert regulatory functions. This also accounts for the paralogue of HPr, Crh.
As a unique function of Crh in B. subtilis, it regulates the flux through the harmful methylglyoxal bypass of the glycolysis. Non-phosphorylated Crh inhibits the enzymatic activity of the key enzyme MgsA by direct protein-protein interaction. Phosphorylation and dephosphorylation of Crh depend on the metabolic state of the cell. In the presence of preferred substrates such as glucose, the FBP level increases within the cell and activates the kinase function of HPrK/P. This results in the formation of Crh~P and subsequently in the release of MgsA from inhibition and thus to activation of the methylglyoxal bypass.
To shed further light into regulation of MgsA we conducted a genetic screen to identify the interaction surface of MgsA and Crh. We isolated several mutants carrying exchanges in the N-terminus of MgsA. All of these mutants show a significantly reduced ability to interact with Crh. Vice versa we restored interaction of Crh. Amino acid exchanges that restore interaction are located within α-helices 1 and 2 of Crh. Proposing a similar mode of action for the interaction of Crh and MgsA, as it was show for all interaction partners of HPr and Crh.
Furthermore, we confirmed the genetic data by X-ray crystallography. The active form of MgsA is a “Trimer of Dimers”. Upon binding of Crh the MgsA complex dissolves into 3 dimers thereby inactivating MgsA.
In addition, we followed the question whether the citric acid cycle and its anaplerotic reaction are essential or not. Based on a series of single and multiple deletion strains of Bacillus subtilis lacking genes that encode for the citric acid cycle and its anaplerotic reaction, we were able to show that these reaction are not essential for live under ideal growth conditions. In this context we focused on the importance of the minor citrate synthase CitA. We obtained strong evidence that CitA is able to compensate for the loss of the major citrate synthase CitZ. | de |
| dc.contributor.coReferee | Görke, Boris PD Dr. | |
| dc.subject.eng | central carbon metabolism | de |
| dc.subject.eng | methylglyoxal synthase | de |
| dc.subject.eng | alternative metabolic pathways | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-9623-4-7 | |
| dc.affiliation.institute | Biologische Fakultät für Biologie und Psychologie | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 835366855 | |