Biosynthesis of Archaebacterial lipids in Halobacterium halobium and Methanobacterium thermoautotrophicum

Abstract

The core membrane lipids in archaebacteria are isoprenoid ether derivatives of glycerol instead of fatty acid esters found in other organisms. Activities for three key enzymes in membrane lipid biosynthesis, isopentenyl diphosphate (IPP) isomerase, geranylgeranyl diphosphate (GGPP) synthase, and 3-0-geranylgeranylglyceryl phosphate (GGGP) synthase were found in the cytosolic fractions of cell-free homogenates from the strict anaerobe Methanobacterium thermoautotrophicum and the extreme halophile Halobacterium halobium. The substrate selectivities of GGGP synthase from both sources were similar and indicate a common pathway for biosynthesis of the isoprenoid compounds in core membrane lipids from methanogenic and halophilic archaebacteria. Archaebacteria are unique organisms that diverged from other life forms at the earliest stages of evolution.lI2 They inhabit normally hostile environments characterized by high salt, low pH, high temperatures, or complete lack of oxygen.2 Archaebacteria also have distinctive biochemical features that include highly diverged 5s and 16s RNAs,= unique metabolic cofactors,@ and novel core membrane lipids.ll3 Archaebacterial membranes consist of glyceryl ethers bearing saturated isoprenoid side chains.1k16 Diethers in thermophilic species are joined covalently at the ends of the isoprene chains to form dimeric membrane spanning tetraethers.11J4 In Methanobacterium thermoautotrophicum the membrane diethers are constructed from (@-glyceryl phosphate (GPP and geranylgeranyl diphosphate (GGPP) by two prenyl transferases. The first, 3-0-geranylgeranylglyceryl phosphate (GGGP) synthase, converts (5')-GP to (SIGGGP, and the second catalyzes alkylation of the secondary hydroxyl in (6')-GGGP by another molecule of GGPP. GGGP synthase strongly prefers (S)-GP as a prenyl acceptor over (R)-GP or dihydroxyacetone phosphate.