Enhanced underground metabolism challenges life at high temperature–metabolic thermoadaptation in hyperthermophilic Archaea

The text-book picture of a perfect, well organised metabolism with highly specific enzymes, is challenged by non-enzymatic reactions and promiscuous enzymes. This, so-called ‘underground metabolism’, is a special challenge for hyperthermophilic Archaea that thrive at temperatures above 80 °C and possess modified central metabolic pathways often with promiscuous enzymes. Hence, the question arises how extremely thermophilic Archaea can operate their unusual metabolism at temperatures where many pathway intermediates are unstable? We herein discuss current insights in the underground metabolism and metabolic thermoadaptation of (hyper)thermophilic Archaea. So far, only a few repair enzymes and salvaging pathways have been investigated in Archaea. Studies of the central carbohydrate metabolism indicate that a number of different strategies have evolved: 1) reduction of the concentration of unstable metabolites, 2) different pathway topologies are used with newly induced enzymes, and 3) damaged metabolites are removed via new metabolic pathways.