Discovery of a metabolic alternative to the classical mevalonate pathway

Elife. 2013 Dec 10:2:e00672. doi: 10.7554/eLife.00672.


Eukarya, Archaea, and some Bacteria encode all or part of the essential mevalonate (MVA) metabolic pathway clinically modulated using statins. Curiously, two components of the MVA pathway are often absent from archaeal genomes. The search for these missing elements led to the discovery of isopentenyl phosphate kinase (IPK), one of two activities necessary to furnish the universal five-carbon isoprenoid building block, isopentenyl diphosphate (IPP). Unexpectedly, we now report functional IPKs also exist in Bacteria and Eukarya. Furthermore, amongst a subset of species within the bacterial phylum Chloroflexi, we identified a new enzyme catalyzing the missing decarboxylative step of the putative alternative MVA pathway. These results demonstrate, for the first time, a functioning alternative MVA pathway. Key to this pathway is the catalytic actions of a newly uncovered enzyme, mevalonate phosphate decarboxylase (MPD) and IPK. Together, these two discoveries suggest that unforeseen variation in isoprenoid metabolism may be widespread in nature. DOI:

Keywords: Archaea; Chloroflexi; Isopentenyl diphosphate; Mevalonate pathway; Mevalonate phosphate decarboxylase; Plants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaea / enzymology
  • Archaea / metabolism
  • Biocatalysis
  • Gas Chromatography-Mass Spectrometry
  • Kinetics
  • Mevalonic Acid / metabolism*
  • Phylogeny
  • Protein Kinases / metabolism


  • Protein Kinases
  • isopentenyl monophosphate kinase
  • Mevalonic Acid