How archaea regulate their energy production from sugars

Over the course of evolution, living organisms have developed different ways of obtaining energy for their own existence from the nutrients available in the environment, such as sugars, in order to maintain their metabolism and ultimately life itself. An important mechanism for this is glycolysis, i.e. the breakdown of sugars such as glucose to generate energy. This process takes place in complex multicellular organisms such as humans as well as in microorganisms. In addition to ‘classic’ bacteria, microorganisms also include archaea, the so-called urbacteria. Most of the latter are adapted to life under extreme environmental conditions, in particular high temperatures of around 100 degrees Celsius, i.e. conditions that prevailed at the beginning of the emergence of life. However, a large number of archaea can also exist in extremely salty or extremely acidic conditions. So-called halophilic archaea are found in salty habitats, for example in natural habitats such as the Dead Sea or man-made environments such as salt production plants. These salt-loving archaea also utilise sugar for their energy production.

At Kiel University, the research group of microbiologist Professor Peter Schönheit is investigating the sugar metabolism of archaea under extreme environmental conditions. In a current research paper, the research team from the Institute for General Microbiology (IfAM) has focused on the group of salt-loving archaea using the model organism Haloferax volcanii as an example. In previous research, the Kiel team was able to identify characteristic pathways of sugar degradation for H. volcanii and many other extremophilic archaea. These pathways represent the sugar degradation pathways at the origin of life. These investigations also revealed differences compared to 'classical' mechanisms of bacteria and multicellular organisms. In a new study, the researchers now investigated the so far largely unknown genetic regulation of sugar degradation in halophilic archaea.  They identified mechanisms responsible for controlling the genes involved in the specific sugar degradation of H. volcanii. Together with researchers from the Medical University of South Alabama and the University of Florida, they recently published their results in the journal Molecular Microbiology.
 

Novel transcriptional regulator of sugar degradation

With their investigations, the researchers identified a regulatory protein in H. volcanii that has evolved from an enzyme that plays a completely different, indispensable role in the metabolism of all living organisms: "The so-called GfcR regulatory protein from H. volcanii has evolved from an enzymatically active protein of the pyrimidine metabolism that is involved in the formation of nucleotides as building blocks of DNA. In this case, it has presumably attained a different function through evolutionary adaptations," emphasises Dr Ulrike Johnsen, first author of the paper. "By fusing with a special element, a so-called DNA-binding domain, it developed into a functional regulatory protein that activates the genes involved in glucose conversion," Johnsen continues.

The research team was also able to identify the mechanism responsible for this: "We were able to identify the so-called KDPG as an inducer molecule for the regulatory protein GfcR, which is formed as an intermediate product during the conversion of glucose to pyruvate in H. volcanii. It induces the function of GfcR as an activator of glucose degradation in H. volcanii. We were able to identify three further inducer molecules for GfcR and discovered that GfcR also regulates the degradation pathways of the sugars D-fructose and D-galactose, as well as for the non-sugar substrate glycerol. For all these substrates, it activates in specific steps of these degradation pathways," explains Johnsen. The researchers were thus able to show that GfcR is not only involved in glucose degradation, but also in the conversion of fructose and galactose as well as another non-sugar-like compound, glycerol. This diverse function indicates a role for GfcR as a global regulator of sugar metabolism in H. volcanii.
 

Universal sugar degradation mechanism in various extremophilic archaea

The Kiel research team, which includes Schönheit and Johnsen as well as Dr Marius Ortjohann and Dr Andreas Reinhardt from the IfAM, was also able to show by bioinformatic analyses that this type of global regulation of sugars and sugar alcohols could also be widespread in other representatives of archaea: "In addition to the salt-loving archaea, it probably also occurs in thermoacidophilic  archaea, which are found in extremely hot and acidic locations. In bacteria and multicellular organisms, on the other hand, this form of sugar degradation and the unique regulation of these degradation pathways is not present," emphasises Schönheit. "The function of GfcR as a regulator for the specific activation of the degradation of various sugars indicates how efficient the sugar metabolism was regulated already in the early stage of evolution," summarises Schönheit.

Overall, the Kiel research team, together with the research groups of structural biologist Professor Christopher Davies from Mobile, Alabama, and molecular biologist Professor Julie Maupin-Furlow from Gainesville, Florida, succeeded in identifying previously unknown details about the genetic regulation of sugar degradation in archaea using the example of H. volcanii.

Research Group Metabolism of Microorganisms,
Institute of General Microbiology, Kiel University
www.mikrobio.uni-kiel.de/de/ag-schoenheit