Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans-anhydromevalonate 5-phosphate

Herein, the partially identified "modified" mevalonate pathway of the majority of archaea is elucidated using information from comparative genomic analysis. Discovery of two enzymes, mevalonate 5-phosphate dehydratase and trans-anhydromevalonate 5-phosphate decarboxylase, from a hyperthermophilic archaeon, Aeropyrum pernix, shows that the pathway passes through a previously unrecognized metabolite, trans-anhydromevalonate 5-phosphate. The distribution of the known mevalonate pathways among archaea and other organisms suggests that the A. pernix-type pathway, which is probably conserved among the majority of archaea, is the evolutionary prototype for the other mevalonate pathways involving diphosphomevalonate decarboxylase or its homologs.