Sulfolobus Systems Biology: Cool hot design for metabolic pathways

Life at high temperature challenges the stability of macromolecules and cellular components, but also the stability of metabolites, which has received little attention. For the cell, the thermal instability of metabolites means it has to deal with the loss of free energy and carbon, or in more extremes, it might result in the accumulation of dead-end compounds. In order to elucidate the requirements and principles of metabolism at high temperature, we used a comparative blueprint modelling approach of the lower part of the glycolysis cycle. The conversion of glyceraldehyde 3-phosphate to pyruvate from the thermoacidophilic Crenarchaeon Sulfolobus solfataricus P2 (optimal growth-temperature 80ºC) was modelled based on the available blueprint model of the eukaryotic model organism Saccharomyces cerevisiae (optimal growth-temperature of 30ºC). In S. solfataricus only one reaction is different, namely glyceraldehyde-3-phosphate is directly converted into 3-phosphoglycerate by the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase, omitting the extremely heat-instable 1,3-bisphosphoglycerate. By taking the temperature dependent non-enzymatic (spontaneous) degradation of 1,3-bisphosphoglycerate in account, modelling reveals that a hot lifestyle requires a cool design.