PT  - JOURNAL ARTICLE
AU  - Luping Liu
AU  - Yike Zou
AU  - Ahanjit Bhattacharya
AU  - Dongyang Zhang
AU  - Susan Q. Lang
AU  - K. N. Houk
AU  - Neal K. Devaraj
TI  - Enzyme-free synthesis of natural phospholipids in water
AID  - 10.1101/746156
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 746156
4099  - http://biorxiv.org/content/early/2019/08/24/746156.short
4100  - http://biorxiv.org/content/early/2019/08/24/746156.full
AB  - All living organisms synthesize phospholipids as the primary constituent of their cell membranes. While phospholipids can spontaneously self-assemble in water to form membrane-bound vesicles, their aqueous synthesis requires pre-existing membrane-embedded enzymes. This limitation has led to models in which the first cells used simpler types of membrane building blocks and has hampered integration of phospholipid synthesis into artificial cells. Here we demonstrate that a combination of ion pairing and self-assembly of reactants allows high-yielding synthesis of cellular phospholipids in water. Acylation of 2-lysophospholipids using cationic thioesters occurs in mildly alkaline solutions resulting in the formation of cell-like membranes. A variety of membrane-forming natural phospholipids can be synthesized. Membrane formation takes place in water from natural alkaline sources, such as soda lakes and hydrothermal oceanic vents. When formed vesicles are transferred to more acidic solutions, electrochemical proton gradients are spontaneously established and maintained.