Evidence of a novel mevalonate pathway in archaea

Biochemistry. 2014 Jul 1;53(25):4161-8. doi: 10.1021/bi500566q. Epub 2014 Jun 18.


Isoprenoids make up a remarkably diverse class of more than 25000 biomolecules that include familiar compounds such as cholesterol, chlorophyll, vitamin A, ubiquinone, and natural rubber. The two essential building blocks of all isoprenoids, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), are ubiquitous in the three domains of life. In most eukaryotes and archaea, IPP and DMAPP are generated through the mevalonate pathway. We have identified two novel enzymes, mevalonate-3-kinase and mevalonate-3-phosphate-5-kinase from Thermoplasma acidophilum, which act sequentially in a putative alternate mevalonate pathway. We propose that a yet unidentified ATP-independent decarboxylase acts upon mevalonate 3,5-bisphosphate, yielding isopentenyl phosphate, which is subsequently phosphorylated by the known isopentenyl phosphate kinase from T. acidophilum to generate the universal isoprenoid precursor, IPP.

Publication types

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

MeSH terms

  • Mevalonic Acid / analogs & derivatives*
  • Mevalonic Acid / metabolism
  • Organophosphates / metabolism*
  • Phosphorylation
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism*
  • Thermoplasma / metabolism*


  • Organophosphates
  • Phosphotransferases
  • Mevalonic Acid