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Researchers shed light on important metabolic pathway

A research team led by microbiologist Dr. David Schleheck, in cooperation with chemists from the University of Konstanz, has discovered how sulpho-glucose is degraded in Escherichia coli bacteria. As this sulphurous glucose analogue is produced by all photosynthetically active organisms, the researchers’ discovery is of great importance for our understanding of the global sulphur cycle.

Sulpho-glucose is produced by all plants and has a similar structure to glucose, a sugar that is far better known than its sulphurous analogue. Sulpho-glucose, which differs from glucose due to the presence of a sulphur group, is found in the chloroplasts of cells, and more precisely, in the lipids of the thylakoid membrane. It was discovered back in 1959 when researchers were able to show that some bacteria use sulpho-glucose as a nutrient and, as a result, are also able to degrade it. However, the mechanism of the underlying biochemical metabolic pathway has remained elusive.  

Ten genes involved in sulpho-glycolysis

Dr. Schleheck's research group at Konstanz University (from left to right): Dieter Spiteller, Michael Weiss, Ann-Katrin Felux, Alasaair Cook, Thomas Huhn, Karin Denger and David Schleheck. Not on the photo: the group's colleagues from Tübingen, Alexander Schneider and Christoph Mayer. © Inka Reiter

Researchers from the University of Konstanz’s Department of Microbial Ecology led by Dr. Schleheck, and supported by colleagues from the Department of Chemistry, have revealed how sulpho-glucose is degraded in E. coli. E. coli is commonly found in human and animal intestines and is the most widely studied model bacterial organism to date. The researchers discovered that the sulpho-glycolysis pathway is encoded by ten genes whose function was previously unknown. “We’ve been able to close another gap in the knowledge about E. coli,” says Dr. Schleheck. “We find it particularly interesting that the sulpho-glycolysis pathway does not involve the same enzymes as the glycolysis pathway.”

Despite the fact that different enzymes from those involved in glycolysis catalyze the degradation of sulpho-glucose, the pathway is nevertheless analogous to that of glucose in that sulpho-glucose is first converted into sulpho-fructose and subsequently into sulpho-fructose phosphate (see Figure). E. coli cannot utilize sulpho-glucose completely; the sulpho-fructose phosphate molecule is cleaved into DHAP, which is used for the generation of energy, and into sulphurous DHPS, which is excreted and degraded by other bacteria in the environment (not shown). “The complete degradation of sulpho-glucose and the recycling of sulphur in the form of inorganic sulphate is the result of cooperation between several bacteria,” says Schleheck. There is evidence that several sulpho-glucose degradation pathways exist and the researchers will analyze these in the future. “Sulpho-glycolysis is one of several sulpho-glucose degradation pathways and we’ve already discovered four new enzymes and three new metabolites associated with this pathway,” says Schleheck.

Cooperation in research

The close cooperation between biologists and chemists from the University of Konstanz was an important aspect of the project. Biologist Karin Denger and Schleheck’s doctoral students Michael Weiss and Ann-Katrin Felux, as well as Prof. Alasdair Cook, did much of the work on microbiological, biochemical, proteomic and molecular analyses. Sulpho-glucose is not commercially available, and was therefore synthesized by Dr. Thomas Huhn from the Department of Chemistry. The pathway intermediates were identified with modern mass spectrometry by doctoral student Alexander Schneider and the chemists Prof. Dr. Christoph Mayer, now at the University of Tübingen, and Prof. Dr. Dieter Spiteller. “The success of the project therefore also highlights the success of research collaborations between biologists and chemists at the University of Konstanz’s Graduate School Chemical Biology, established as part of the German Excellence Initiative,” says Schleheck.

The schematic shows the biochemical degradation pathway of sulpha-glucose in Escherichia coli.
Sulpho-glucose is taken up by Escherichia coli and degraded in the same way as glucose (glycolysis); sulpho-fructose phosphate is cleaved into DHAP, which is used to generate energy and cell growth. The sulphurous DHPS intermediate cannot by utilized by E. coli and is excreted. It is mineralized by other bacteria using a well-known metabolic pathway (not shown). © David Schleheck

Importance of sulpho-glucose for humans and the environment

The results of the Konstanz researchers are not only relevant for botany, but also for human biology since E. coli is an important and valuable inhabitant of the human intestinal tract where plant nutrition also provides sulpho-glucose as a so far overlooked source of nutrients for this bacterium. The sulpho-glycolysis pathway is also found in other enterobacteria, including in pathogenic bacteria such as Salmonella and Klebsiella.

Algae also have a sulpho-glycolysis pathway; these organisms use sulpho-glucose as an internal source of sulphur during periods of sulphur deficiency. However, there is no indication that sulpho-glucose can be metabolized directly by animals or humans, only indirectly by intestinal bacteria such as E. coli. “Nevertheless, a study carried out by another research group suggests that sulpho-glucose might – although only indirectly – have a positive impact on the human sugar metabolism, especially in people who live on a vegetarian diet,” says Dr. Schleheck.

The annual production of natural sulpho-glucose is estimated at around ten billion tonnes and sulpho-glucose is present in all plants, mosses, ferns, algae and bacteria. The bacterial degradation of sulpho-glucose is an important component of the material cycles in ecosystems, in particular in the global sulphur cycle. Knowledge about the degradation of sulpho-glucose and the enzymes and genes involved provides researchers with greater understanding of the corresponding metabolic processes in plants and algae. “The thorough understanding of sulphur recycling in plants and the complete degradation of sulpho-glucose by soil bacteria is of crucial importance as plants that are grown in European soils are increasingly suffering from sulphur deficiency. This is due to the successful reduction of acid rain,” concludes Dr. Schleheck.

Further information:
Dr. David Schleheck
University Konstanz
Tel.: +49 (0)7531 88-3270
E-mail: david.schleheck(at)uni-konstanz.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/researchers-shed-light-on-important-metabolic-pathway