The archaea are distinguished by their unique isoprenoid ether lipids, which typically consist of the basic sn-2,3-diphytanylglycerol diether (archaeol) and sn-2,3-dibiphytanyldiglycerol tetraether (caldarchaeol) core with a variety of polar headgroups. Many hyperthermophilic archaea synthesize tetraether lipids with up to 4 cyclopentane rings incorporated into each of the 40-carbon chains presumably to improve membrane thermal stability thereby contributing to survival at temperatures up to ~110 °C. The biosynthetic pathway for the archaeal membrane ether lipids exhibits unprecedented isoprenoid chemistry, in particular, the head-to-head attachment of isoprenoid intermediates.

This study aimed to investigate the isoprenoid ether lipid biosynthesis pathway, including tetraether lipid synthesis in the hyperthermophilic archaeon, Archaeoglobus fulgidus. Utilizing the lipid synthesis machinery of A. fulgidus, an engineered E. coli strain was constructed in an effort to demonstrate efficient, high throughput isoprenoid ether lipid biosynthesis from simple metabolites. The synthesis of the intermediate geranylgeranylglyceryl phosphate (GGGP) has been accomplished by cloning and expressing the A. fulgidus genes sn-glycerol-1-phosphate (G1P) dehydrogenase, geranylgeranyl diphosphate (GGPP) synthase, and GGGP synthase, under the control of the araBAD promoter. This strain also includes the overexpression of the native E. coli gene, idi (IPP isomerase), previously shown to improve carotenoid biosynthesis, which shares common precursors with the isoprenoid ether lipid pathway.