Many anaerobic hyperthermophilic archaea, considered to represent the most ancestral living organisms, degrade glucose to acetate as major fermentation product. The degradation involves modified Embden-Meyerhof (EM) pathways, which differ from the classical EM pathway by the presence of several novel enzymes and enzyme families catalysing e.g. the phosphorylation of glucose and of fructose 6-phosphate, the isomerization of glucose 6-phosphate and the oxidation of glyceraldehyde 3-phosphate. Further, ATP-dependent 6-phosphofructokinases (ATP-PFKs) and pyruvate kinases (PKs) in hyperthermophilic archaea, i.e. canonical sites of allosteric control in bacteria and eukarya, do not respond to any known allosteric effectors (1). Finally, the conversion of acetyl-CoA to acetate, which represents a major energy conserving site in archaeal sugar fermentation, is catalyzed by a novel prokaryotic enzyme, ADP-forming acetyl-CoA synthetase (acetyl-CoA + ADP + P_i acetate + ATP + CoA) (2) The modified EM pathways and their enzymes, the allosteric properties of archaeal ATP-PFK and PKs and the mechanism of acetate formation will be described in comparison to the enzymes of the hyperthermophilic bacterium Thermotoga maritima, which also ferments glucose to acetate. The crystal structure of PK from the hyperthermophilic archaeon Pyrobaculum aerophilum was solved resulting in the identification of a novel type of allosteric activator (3). Together, the data indicate that the unusual features of archaeal glycolysis and of acetate formation are due to their phylogeny rather than to an adaptation to a hyperthermophilic life style

1. Siebers, B. and Schönheit, P. (2005) Curr. Opin. Microbiol.8, 695-705
2. Bräsen et al. (2008) J. Biol. Chem. 283, 15409-15418
3. Solomons J.T. et al. (2013) Biochemistry.52, 5865-75.