Ji Peng, Harjung Alexander, Knittel Caroline H, Fracassi Alessandro, Chen Jiyue, Brea Roberto J, Devaraj Neal K
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Nat Commun. 2025 May 31;16(1):5068. doi: 10.1038/s41467-025-60358-4.
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.
脂质合成在细胞结构、信号传导和新陈代谢中起着核心作用。一种用于天然脂质非生物合成的通用方法可以改变逼真的人造细胞的发展，并开启探索活细胞中脂质功能的新途径。在这里，我们展示了利用可见光驱动的光氧化还原化学在水中非生物形成天然脂质。碳氢化合物尾巴与极性单链前体的自由基介导偶联产生了与酶促形成的脂质相同的脂质。时空控制的脂质生成促进了从头开始的囊泡形成、生长和分裂。脂质合成可以由特异性结合并激活光催化剂的RNA适体驱动，从而在非生物脂质代谢和核酸序列之间建立直接联系。生物活性脂质的光介导组装可以在活细胞中发生，引发诸如细胞凋亡和蛋白激酶C（PKC）激活等信号事件。我们发现光化学脂质合成可以由简单的遗传元件驱动，这可能是开发能够进行达尔文进化的原始细胞的起点。此外，在活细胞中以精确的时空控制产生特定膜脂质的能力将推动关于脂质结构如何影响细胞功能的研究。
