Biosynthesis and Evolution of Archaeal Membranes and Ether Phospholipids

  • Yosuke Koga
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


The fundamental biosynthetic pathway of archaeal phospholipids has been elucidated by in vitro studies based on comparison with the bacterial phospholipid biosynthesis pathway in bacteria. The glycerophosphate (sn-glycerol-1-phosphate; G1P) backbone of archaeal phospholipids (an enantiomer of bacterial sn-glycerol-3-phosphate; G3P) is formed from dihydroxyacetonephosphate (DHAP) catalyzed by a novel enzyme, G1P dehydrogenase. Isoprenoid chains are synthesized either by one of the classical or modified mevalonate pathways. The first ether bond is formed at the sn-3 position of the G1P backbone by a soluble enzyme geranylgeranylglycerophosphate (GGGP) synthase. G1P dehydrogenase is specific for G1P. GGGP synthase involves the step where three major characteristics of archaeal phospholipid structure are fixed into one molecule. Therefore, this enzyme can be regarded as “a quality control mechanism” in the biosynthesis of archaeal membrane lipid. Digeranylgeranylglycerophosphate (DGGGP) synthase catalyzes the formation of a second ether bond between the G1P backbone and an isoprenoid chain. The DGGGP synthase belongs to the hydrophobic ring-forming prenyltransferase enzyme family. The core lipid is activated by CTP catalyzed by CDP-archaeol synthase. Subsequently, CMP is replaced in CDP-archaeol by L-serine or other polar head groups. The entire pathway of phospholipid biosynthesis (starting from DHAP to the synthesis of one of amphiphilic phospholipids) in Archaea is quite similar to the bacterial pathway. It is especially remarkable that serine phospholipid and inositol phospholipid synthases from archaea and bacteria show unusually broad substrate specificities. These enzymes display nearly the same level of specific activities with all the substrates, CDP-activated core lipids of the archaeal or bacterial types (sn-2,3-diphytanyl glycerol-1-phosphate, Ai or sn-1,2-diacyl glycerol-3-phosphate, Bf) or with unnatural types (sn-2,3-diacyl glycerol-1-phosphate, Af or sn-1,2-diphytanyl glycerol-3-phosphate, Bi). In particular, the entire archaeal lipid biosynthesis pathway and the broad substrate specificity displayed by the enzymes involved suggest that in the ancient times, one enzyme reacted with various compounds including lipid-like compounds that had been formed abiotically. In the primitive lipid biosynthetic pathway, a variety of similar lipids was produced with the catalysis by a small number of catalysts with a broad substrate specificity. Although innumerous lipid components were abiotically synthesized, most of these lipids did not persist. The abundant lipid compounds included Ai, Bf, Af, and Bi. Presently, we can observe a large variety of amphiphilic phospholipids which constitute cellular membranes. The extremely broad substrate specificity of polar head group-attaching enzymes suggests that the differentiation of one pathway into two pathways, a bacterial and an archaeal, occurred.

These phenomena lead to the hypothesis that postulates the existence of a promiscuous stage, a historical stage during which a complex mixture of the isomers of the lipid components coexisted. Nowadays, archaeal and bacterial membrane lipids consist exclusively of the Ai core and Bf core, respectively. This fact implies that biological differentiation was driven by membrane segregation.



sn-2,3-Diphytanyl Glycerol-1-phosphate


sn-1,2-Diacyl Glycerol-3-phosphate


sn-2,3-Diacyl Glycerol-1-phosphate


sn-1,2-Diphytanyl Glycerol-3-phosphate



The author greatly indebted to Prof. Otto Geiger for his excellent help in the last stage of preparing of this manuscript, and wishes to thank to Prof. Hiroyuki Morii for his help in preparing figures and to Dr. Yuichi Koga for his help in rearrangement of the manuscript.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University of Occupational and Environmental HealthKitakyushu CityJapan
  2. 2.Munakata City, FukuokaJapan

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