Abstract
Most archaeal groups and deeply branching bacterial lineages harbour thermophilic organisms with a chemolithoautotrophic metabolism. They live at high temperatures in volcanic habitats at the expense of inorganic substances, often under anoxic conditions1. These autotrophic organisms use diverse carbon dioxide fixation mechanisms generating acetyl-coenzyme A, from which gluconeogenesis must start2,3,4. Here we show that virtually all archaeal groups as well as the deeply branching bacterial lineages contain a bifunctional fructose 1,6-bisphosphate (FBP) aldolase/phosphatase with both FBP aldolase and FBP phosphatase activity. This enzyme is missing in most other Bacteria and in Eukaryota, and is heat-stabile even in mesophilic marine Crenarchaeota. Its bifunctionality ensures that heat-labile triosephosphates are quickly removed and trapped in stabile fructose 6-phosphate, rendering gluconeogenesis unidirectional. We propose that this highly conserved, heat-stabile and bifunctional FBP aldolase/phosphatase represents the pace-making ancestral gluconeogenic enzyme, and that in evolution gluconeogenesis preceded glycolysis5.
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Acknowledgements
We thank R. Thauer, S. Ragsdale, H. Atomi and H. Huber for the supply of strains; F. Drepper for help with bioinformatic approaches; W. Haehnel and B. Knapp for MS analysis; N. Gad’on and C. Ebenau-Jehle for growing cells and maintaining the laboratory running; the DOE Joint Genome Institute for early release of archaeal genomic sequence data; and the Deutsche Forschungsgemeinschaft and Evonik-Degussa for financial support. We also thank M. Ziemski and I. Berg for help with data base analysis as the basis of Fig. 1a, and H. Teeling and F. O. Glöckner for providing Fig. 1b.
Author Contributions R.F.S. performed the experiments; R.F.S. and G.F. designed the work and wrote the paper.
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Say, R., Fuchs, G. Fructose 1,6-bisphosphate aldolase/phosphatase may be an ancestral gluconeogenic enzyme. Nature 464, 1077–1081 (2010). https://doi.org/10.1038/nature08884
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DOI: https://doi.org/10.1038/nature08884
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