RRC ID 34250
Author Azami Y, Hattori A, Nishimura H, Kawaide H, Yoshimura T, Hemmi H.
Title (R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum.
Journal J. Biol. Chem.
Abstract 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.
Volume 289(23)
Pages 15957-67
Published 2014-6-6
DOI 10.1074/jbc.M114.562686
PII M114.562686
PMID 24755225
PMC PMC4047369
MeSH Adenosine Triphosphate / metabolism Archaeal Proteins / genetics Archaeal Proteins / metabolism Base Sequence Cell-Free System Chromatography, Ion Exchange Chromatography, Thin Layer DNA Primers Mevalonic Acid / analogs & derivatives* Mevalonic Acid / metabolism* Phylogeny Thermoplasma / metabolism*
IF 4.011
Times Cited 9
General Microbes JCM 9062