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Journal Article

A minimal biochemical route towards de novo formation of synthetic phospholipid membranes

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Bhattacharya, A., Brea, R. J., Niederholtmeyer, H., & Devaraj, N. K. (2019). A minimal biochemical route towards de novo formation of synthetic phospholipid membranes. NATURE COMMUNICATIONS, 10: 300. doi:10.1038/s41467-018-08174-x.

Cite as: https://hdl.handle.net/21.11116/0000-000A-6F34-0
All living cells consist of membrane compartments, which are mainly composed of phospholipids. Phospholipid synthesis is catalyzed by membrane-bound enzymes, which themselves require pre-existing membranes for function. Thus, the principle of membrane continuity creates a paradox when considering how the first biochemical membrane-synthesis machinery arose and has hampered efforts to develop simplified pathways for membrane generation in synthetic cells. Here, we develop a high-yielding strategy for de novo formation and growth of phospholipid membranes by repurposing a soluble enzyme FadD10 to form fatty acyl adenylates that react with amine-functionalized lysolipids to form phospholipids. Continuous supply of fresh precursors needed for lipid synthesis enables the growth of vesicles encapsulating FadD10. Using a minimal transcription/translation system, phospholipid vesicles are generated de novo in the presence of DNA encoding FadD10. Our findings suggest that alternate chemistries can produce and maintain synthetic phospholipid membranes and provides a strategy for generating membrane-based materials.