Photochemical synthesis of natural lipids in artificial and living cells

Peng Ji, Alexander Harjung, Caroline H. Knittel, Alessandro Fracassi, Jiyue Chen, Roberto J. Brea and Neal K. Devaraj ()
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Peng Ji: University of California, San Diego
Alexander Harjung: University of California, San Diego
Caroline H. Knittel: University of California, San Diego
Alessandro Fracassi: University of California, San Diego
Jiyue Chen: University of California, San Diego
Roberto J. Brea: University of California, San Diego
Neal K. Devaraj: University of California, San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Lipid synthesis plays a central role in cell structure, signaling, and metabolism. A general method for the abiogenesis of natural lipids could transform the development of lifelike artificial cells and unlock new ways to explore lipid functions in living cells. Here, we demonstrate the abiotic formation of natural lipids in water using visible-light-driven photoredox chemistry. Radical-mediated coupling of hydrocarbon tails to polar single-chain precursors yields lipids identical to those enzymatically formed. Spatiotemporally controlled lipid generation promotes de novo vesicle formation, growth, and division. Lipid synthesis can be driven by RNA aptamers that specifically bind and activate photocatalysts, establishing a direct link between abiotic lipid metabolism and nucleic acid sequence. Light-mediated assembly of bioactive lipids can take place in living cells, triggering signaling events such as apoptosis and protein kinase C (PKC) activation. Our finding that photochemical lipid synthesis can be driven by simple genetic elements could be the starting point for developing protocells capable of Darwinian evolution. Additionally, the ability to generate specific membrane lipids in living cells with precise spatiotemporal control will advance studies on how lipid structure influences cellular function.

Date: 2025
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DOI: 10.1038/s41467-025-60358-4

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