Research team from Kiel University’s microbiology discovers hitherto unknown regulation of sugar degradation in primordial bacteria
In the course of the earth's history, all living beings have developed strategies to gain energy for their existence from food and thus make life possible. Even today, complex multicellular organisms use the same mechanisms that simple organisms use for their metabolism. A central element is glycolysis, i.e. the splitting of sugars to gain energy. But how did this metabolic pathway develop at the beginning of the Earth's history? And what are the general differences in the regulation of glycolytic degradation pathways?
Scientists agree that life originated probably about three and a half billion years ago in hot volcanic springs. The living conditions in this proverbial primeval soup have little in common with our environment today: Extremely high temperatures, the absence of light, oxygen and organic compounds are best described as hostile to life. Nevertheless, simple and original organisms such as the so-called hyperthermophilic archaea, the primordial bacteria, were able to thrive in this environment. These simple organisms can still be found, for example, in the hydrothermal springs of the deep sea. They need heat, i.e. temperatures around 100° Celsius, and only simple volcanic gases such as hydrogen, carbon dioxide and sulphur to grow. However, these primarordial bacteria are also able to use organic substances such as sugar to generate energy. A research team from the Institute of General Microbiology at the Kiel University, led by Professor Peter Schönheit, has recently discovered a previously unknown path of glycolysis and its regulation in these hyperthermophilic archaea. Using the example of primordial bacteria, the scientists from Kiel have now been able to show how this evolutionarily original mechanism of sugar degradation functions, how it is regulated and which molecular players are involved. They recently published their novel results in the renowned biochemical journal The FEBS Journal of the Federation of European Biochemical Societies (FEBS).
Sugar degradation as a central metabolic element
Most organisms living today, from simple microbes to highly developed multicellular organisms including humans, degrade sugar, for example the simple sugar glucose, in a basically identical, so to speak 'classical' way, the so-called glycolysis. The primordial bacteria, the hyperthermophilic archaea, degrade sugar via modified variants of classical glycolysis. These glycolytic degradation pathways involve various enzymes that store and make available energy in the form of the universal energy carrier adenosine triphosphate (ATP). The speed of the ATP formation processes depends on the energy state of the cell: If there is a lack of energy, individual enzymes, in particular the so-called pyruvate kinase, are activated. Which molecules trigger this activation has long been known for the classical form of glycolysis. The pyruvate kinase of many microorganisms and humans is activated by the phosphorylated sugar fructose bisphosphate.
The research group at the Institute of General Microbiology has been investigating the processes of sugar metabolism of hyperthermophilic primordial bacteria for many years under Schönheit’s direction. They have described previously unknown degradation pathways and discovered the involvement of a large number of novel enzymes. However, it was still unclear which building block is responsible for the activation of pyruvate kinase in the archaea, and fructose bisphosphate could be excluded as an activator. "Now we have finally succeeded in identifying the missing piece of the puzzle in the sugar degradation of the primordial bacteria," said a delighted microbiologist Peter Schönheit. "The analysis of the crystal structure of the pyruvate kinase of a certain type of primordial bacteria, Pyrobaculum aerophilum, provided the decisive indication of the hitherto unknown activator, the so-called 3-phosphoglycerate", continued Schönheit.
The research team, including first author Dr Ulrike Johnsen and Dr Andreas Reinhardt from the Schönheit’s research group, structural biologist Professor Christopher Davies from the Medical University of South Carolina, and Kiel University’s bioinformaticians Dr Giddy Landan and Dr Fernando Tria, was able to show that this newly described form of regulation of pyruvate kinases has a broad distribution within primordial bacteria. "Sugar degradation in primordial bacteria is regulated by a completely different activator, a phosphorylated acid-3-phosphoglycerate. This regulator is adapted to the peculiarities of archaic glycolysis and is not effective in classical glycolysis," said Dr. Ulrike Johnsen, a researcher in the Schönheit’s group and first author of the paper.
The evolution of metabolism
The now successful elucidation of the activation mechanism of sugar degradation in the archaea also allows new insights into the course of the early developmental history of life. The comparison of the phylogenetic relationships of differently complex organisms suggests that different mechanisms of sugar degradation may have developed several times and independently of each other during evolution. In adaptation to changing environmental conditions, such as the absence of light and air in the hot springs of prehistoric times or the sudden mass availability of sugar as a result of the newly evolved photosynthesis, evolution has produced this ability in various forms. The hyperthermophilic primordial bacteria, which may have been the first living organisms with this metabolic property, were particularly early in the process.
Schönheit's work on alternative ways of sugar degradation in archaic organisms thus contributes significantly to the understanding of the early development of life and the associated metabolic processes. Together with his team, he is continuing a classical and successful field of research at Kiel University: At the beginning of the 20th century, Professor Otto Meyerhof researched the mechanisms of energy conversion in cells in Kiel and described the classical mechanism of glycolysis in multicellular organisms for the first time. In 1922, Meyerhof was awarded the Nobel Prize for Medicine for this groundbreaking discovery.
Ulrike Johnsen, Andreas Reinhardt, Giddy Landan, Fernando D. K. Tria, Jonathan M. Turner, Christopher Davies, Peter Schönheit (2019): New views on an old enzyme: allosteric regulation and evolution of archaeal pyruvate kinases. The FEBS Journal DOI: 10.1111/febs.14837
Research Group Metabolism of Microorganisms, Institute of General Microbiology, Kiel University