Identification of CDP-Archaeol Synthase, a Missing Link of Ether Lipid Biosynthesis in Archaea

• Published in: Chemistry & biology Vol. 21; no. 10; pp. 1392 - 1401
• Main Authors: Jain, Samta, Caforio, Antonella, Fodran, Peter, Lolkema, Juke S., Minnaard, Adriaan J., Driessen, Arnold J.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 23.10.2014
• Subjects: Archaea - enzymology; Archaeal Proteins - chemistry; Archaeal Proteins - genetics; Archaeal Proteins - metabolism; Computational Biology; Escherichia coli - metabolism; Ethers - chemistry; Glyceryl Ethers - chemistry; Glyceryl Ethers - metabolism; Lipids - biosynthesis; Lipids - chemistry
• ISSN: 1074-5521; 1879-1301
• DOI: 10.1016/j.chembiol.2014.07.022

Archaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane protein CDP-archaeol synthase (CarS) that catalyzes the transfer of the nucleotide to its specific archaeal lipid substrate, leading to the formation of a CDP-activated precursor (CDP-archaeol) to which polar head groups are attached. The discovery of CarS enabled reconstitution of the entire archaeal lipid biosynthesis pathway in vitro, starting from simple isoprenoid building blocks and using a set of five purified enzymes. The cell free synthetic strategy for archaeal lipids we describe opens opportunity for studies of archaeal lipid biochemistry. Additionally, insights into archaeal lipid biosynthesis reported here allow addressing the evolutionary hypothesis of the lipid divide between Archaea and Bacteria. [Display omitted] •Identification and characterization of a key archaeal lipid synthesis enzyme, CarS•CarS activates membrane lipid precursor (DGGGP) for polar head group attachment•CarS recognizes archaetidic acid, but not phosphatidic acid•One-pot synthesis of ether lipid CDP-archaeol is achieved using five purified enzymes Archaeal membranes contain unique lipids featuring an ether link between glycerol and linear isoprenoids. Jain et al. identify a conserved membrane protein, CarS, responsible for biosynthesis of the central intermediate CDP-archaeol, and achieve in vitro reconstitution of the entire lipid biosynthesis pathway.