# The Cell Membrane of _Sulfolobus_ spp.--Homeoviscous Adaption and Biotechnological Applications
## 2 Cell Membrane and Lipids of _Sulfolobus_ Spp.
### Biosynthesis of Archaeal Membrane Lipids  
The biosynthesis of membrane lipids is different between the tree domains of life, as well as within one domain. In general, archaeal membrane lipids are formed by multiple consecutive enzymatic steps (Figure 3), starting with the synthesis of the isoprenoid building blocks isopentyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). This is done via the MEP/DOXP pathway, the classical mevalonate (MVA) or the alternate MVA pathway. The alternate MVA pathway is most common in Archaea, with the exception of Sulfolobales that utilize the classical MVA pathway [50]. According to [PERSON] et al., _Sulfolobus_ acquired the enzymes of the classical MVA pathway through lateral gene transfer from Eukaryotes [51]. Furthermore, geranyl diphosphate (GPP) is formed through condensation reactions of DMAPP and IPP. The carbon 10 compound is then condensed with several IPP molecules, to form farnesyl (C15), geranylgeranyl (C20) or farnesylgeranyl (C25) diphosphate [52]. For the formation of the characteristic ether bonded geranylgeranylglycerol diphosphate (GGGP), geranylgeranyl diphosphate (GGPP) of the pathway described before is needed, as well as glycerol-1-phosphate. The latter is formed through the reduction of dihydroxyacetone phosphate (DHAP), utilizing NADH. The diether DGGGP (2,3-O-geranylgeranylglycerol diphosphate) is formed by GGGP and GGPP. With this step, the core lipid is formed and is activated by cytidine triphosphate (CTP) in the following. This is done by the CDP archaeol synthase [50; 53]. Figure 3: Pathway of archaeal lipid biosynthesis. MVA, mevalonate pathway; IPP, isopentyl pyrophosphate; DMAPP, dimethylallyl pyrophosphate; GGPP, geranylgeranyl diphosphate; ED pathway, Entner-Doudoroff pathway; GAP, glyceraldehyde 3-phosphate; TIM, triosophosphate isomerase; DHAP, dihydroxyacetone phosphate; G1P, glycerol-1-phosphate; GGGP, geranylgeranylglycerol phosphate; DGGGP, 2,3-O-geranylgeranylglycerol diphosphate; CTP, cytidine triphosphate; CMP, cytidine monophosphate; CDP, cytidine diphosphate; AIP archaeidylinositol phosphate; AI, archaeidylinositol; IP-DEL inositolphosphate diether lipid; TEL, tetraether lipid; P, phosphate; PP, pyrophosphate. A description of the biosynthesis steps is given in the text. Figure based on [50; 54]. Next, the reactive cytidine diphosphate (CDP) head group is replaced by polar head groups, such as serine, ethanolamin, glycerol or _myo_-inositol. Then, geranylgeranyl reductases catalyze the hydrogenation of the unsaturated DGGGP and hence completing the structure of the archaeal [50]. It is still not clear at which step the saturation occurs. However, [PERSON] and [PERSON] (2007) proposed that it took place after the addition of the polar head group [52]. The caldarchaeol, which represents the characteristic tetraether lipid structure, is formed from two archaeols undergoing a head to head condensation. This was proven by labeling experiments in _Thermoplasma acidophilum_[50]. Until now, the enzyme catalyzing the tetraether bond has not been identified. Additionally, the biosynthesis of cyclopentane rings is also only partially known. A hypothesis about tetraether and cyclopentane ring formation was offered by [PERSON] et al. They suggested a \"multiple-key, multiple-lock\" mechanism and proposed that the cyclopentane rings are being formed before the tetraethers configuration. The coupling of two diethers is hypothetically realized by phytoene synthase, which has been elucidated in the archaeal genome. However, this theory still has to be verified by experiments [55]. A strong argument against this hypothesis is that the ring index (RI) quickly changes upon changed environmental conditions [46]. Following the hypothesis from [PERSON], a change in the ring number would require a complete cycle of lipid degradation and synthesis of the new lipids with different ring numbers. The findings by [PERSON] et al.