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.