Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Nat Chem. 2020 Nov;12(11):1029-1034. doi: 10.1038/s41557-020-00559-0. Epub 2020 Oct 12.
All living organisms synthesize phospholipids as the primary constituent of their cell membranes. Enzymatic synthesis of diacylphospholipids requires preexisting membrane-embedded enzymes. This limitation has led to models of early life 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 an enzyme-free synthesis of natural diacylphospholipids by transacylation in water, which is enabled by a combination of ion pairing and self-assembly between lysophospholipids and acyl donors. A variety of membrane-forming cellular phospholipids have been obtained in high yields. 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. This high-yielding non-enzymatic synthesis of natural phospholipids in water opens up new routes for lipid synthesis in artificial cells and sheds light on the origin and evolution of cellular membranes.
所有生物体都将磷脂合成为细胞膜的主要成分。二酰基磷脂的酶促合成需要预先存在的膜嵌入酶。这种局限性导致了早期生命的模型，其中第一个细胞使用更简单类型的膜构建块，并阻碍了磷脂合成到人工细胞中的整合。在这里，我们通过水相中的转酰基反应展示了天然二酰基磷脂的无酶合成，这得益于溶血磷脂和酰基供体之间的离子配对和自组装的组合。已经以高产率获得了多种形成膜的细胞磷脂。在天然碱性来源（如苏打湖和热液海洋喷口）的水中形成膜。当形成的囊泡转移到更酸性的溶液中时，电化学质子梯度会自动建立和维持。这种在水中高产率的非酶法天然磷脂合成开辟了人工细胞中脂质合成的新途径，并阐明了细胞膜的起源和进化。
