(R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum.

The lack of a few conserved enzymes in the classical mevalonate pathway and the widespread existence of isopentenyl phosphate kinase suggest the presence of a partly modified mevalonate pathway in most archaea and in some bacteria. In the pathway, (R)-mevalonate 5-phosphate is thought to be metabolized to isopentenyl diphosphate via isopentenyl phosphate. The long anticipated enzyme that catalyzes the reaction from (R)-mevalonate 5-phosphate to isopentenyl phosphate was recently identified in a Cloroflexi bacterium, Roseiflexus castenholzii, and in a halophilic archaeon, Haloferax volcanii. However, our trial to convert the intermediates of the classical and modified mevalonate pathways into isopentenyl diphosphate using cell-free extract from a thermophilic archaeon Thermoplasma acidophilum implied that the branch point intermediate of these known pathways, i.e. (R)-mevalonate 5-phosphate, is unlikely to be the precursor of isoprenoid. Through the process of characterizing the recombinant homologs of mevalonate pathway-related enzymes from the archaeon, a distant homolog of diphosphomevalonate decarboxylase was found to catalyze the phosphorylation of (R)-mevalonate to yield (R)-mevalonate 3-phosphate. The product could be converted into isopentenyl phosphate, probably through (R)-mevalonate 3,5-bisphosphate, by the action of unidentified T. acidophilum enzymes fractionated by anion-exchange chromatography. These findings demonstrate the presence of a third alternative "Thermoplasma-type" mevalonate pathway, which involves (R)-mevalonate 3-phosphotransferase and probably both (R)-mevalonate 3-phosphate 5-phosphotransferase and (R)-mevalonate 3,5-bisphosphate decarboxylase, in addition to isopentenyl phosphate kinase.

Biochemical evidence supporting the presence of the classical mevalonate pathway in the thermoacidophilic archaeon Sulfolobus solfataricus.

The existence of the classical mevalonate (MVA) pathway was examined in the thermoacidophilic archaeon Sulfolobus solfataricus. The pathway is considered uncommon among archaea because the genes of the orthologues of phosphomevalonate kinase (PMK) and/or diphosphomevalonate decarboxylase (DMD) are absent in the genomes of most archaea. Instead, the modified MVA pathway, which involves isopentenyl phosphate kinase (IPK), has been proposed to exist in the archaea that lack the classical pathway. However, some archaea including S. solfataricus possess the genes of the orthologues of both IPK and all enzymes of the classical pathway. Biochemical characterization using recombinant proteins showed that the orthologues of the enzymes catalyzing the late steps of the classical pathway, i.e. MVA kinase, PMK and DMD, are all active. Moreover, in vitro conversion of the intermediates in the classical and modified pathways by cell-free extract from S. solfataricus indicated that only the classical pathway likely works in the organism.