Discovery of a Novel Mevalonate Pathway and its Potential to Produce Biofuels

The mevalonate pathway is present in eukaryotes, archaea, and some bacteria, where it produces the building blocks used to make cholesterol, vitamin A, natural rubber, and over 25,000 other biomolecules collectively called isoprenoids. Here we report the discovery of a novel mevalonate pathway in archaea. We describe the identification and characterization of three new enzymes, two new metabolites, a novel structure, and a new mechanism. We also show that the new pathway is unique to extreme acidophiles that grow below pH 2. We attempt to re-design three mevalonate pathway enzymes (mevalonate 3-kinase, mevalonate 5-phosphate decarboxylase, and mevalonate 5-pyrophosphate decarboxylase) to produce isoprenol through the decarboxylation of mevalonate. Isoprenol is a 5-carbon alcohol that has a higher energy density than ethanol. Both rational design and random mutagenesis strategies are described. Finally, we report a new method for the soluble expression of recombinant proteins in E. coli through the co-expression of archaeal thermosomes and prefoldins.