Extended Data Fig. 1: Saturated and unsaturated biosynthesis pathways for biphytanyl chain formation in macrocyclic Archaeol and GDGT.
From: Discovery, structure and mechanism of a tetraether lipid synthase
Archaeal membrane lipid biosynthesis is well established through formation of the fully saturated diether lipid Archaeol. However, how the biphytanyl chain is formed is unknown. Two potential pathways for generating the biphytanyl chain have been proposed: a pathway involving a saturated substrate and a pathway involving an unsaturated substrate, both of which entail the formation of a Csp3-Csp3 bond between the termini of two lipid chains. The distinction between the two routes, however, is when the biphytanyl chain is formed in relation to saturation of the lipid chain by geranylgeranyl reductase (GGR). In the unsaturated route, the biphytanyl chain is formed prior to chain saturation by GGR. Therefore, the substrate for the reaction is an unsaturated lipid: digeranylgeranyl glycerol phosphate (DGGGP) with R=H or a polar headgroup. In the saturated route, the fully saturated lipid is formed by GGR-mediated chain reduction prior to biphytanyl chain formation. Therefore, the substrate for the reaction contains fully saturated chains: archaeol when R=H and archaetidylglycerol when R=glycerol. Abbreviations: dimethylallyl diphosphate (DMAPP), isopentenyl pyrophosphate (IPP), geranylgeranyl pyrophosphate synthase (GGPP synthase), geranylgeranyl pyrophosphate (GGP), sn-glycerol-1-phosphate (G1P), geranylgeranyl glycerol phosphate (GGGP), digeranylgeranyl glycerol phosphate (DGGGP), cytidine diphosphate (CDP), glycerol dibiphytanyl glycerol tetraether (GDGT).
