Chen Po-Hsun Brian, Li Xiang-Ling, Baskin Jeremy M
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, United States.
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Chem Rev. 2025 Feb 26;125(4):2502-2560. doi: 10.1021/acs.chemrev.4c00761. Epub 2025 Jan 13.
Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, and many interactions with other biomolecules have justly earned lipids a reputation as a vexing class of molecules to understand. Further, as the cell's hydrophobic metabolites, lipids assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions. Motivated by this daunting complexity, researchers across disciplines are bringing order to the seeming chaos of biological lipids and membranes. Here, we formalize these efforts as "synthetic lipid biology". Inspired by the idea, central to synthetic biology, that our abilities to understand and build biological systems are intimately connected, we organize studies and approaches across numerous fields to create, manipulate, and analyze lipids and biomembranes. These include construction of lipids and membranes from scratch using chemical and chemoenzymatic synthesis, editing of pre-existing membranes using optogenetics and protein engineering, detection of lipid metabolism and transport using bioorthogonal chemistry, and probing of lipid-protein interactions and membrane biophysical properties. What emerges is a portrait of an incipient field where chemists, biologists, physicists, and engineers work together in proximity─like lipids themselves─to build a clearer description of the properties, behaviors, and functions of lipids and membranes.
细胞含有数千种不同的脂质。它们快速且冗余的代谢、动态运动以及与其他生物分子的诸多相互作用,理所当然地使脂质成为一类难以理解的分子。此外,作为细胞的疏水代谢产物,脂质组装成超分子结构——最常见的是双层膜或细胞膜——并从中执行无数生物学功能。受这种令人望而生畏的复杂性驱使,各学科的研究人员正在为生物脂质和膜看似混乱的局面带来秩序。在此,我们将这些努力形式化为“合成脂质生物学”。受合成生物学核心思想的启发,即我们理解和构建生物系统的能力紧密相连,我们整合了众多领域的研究和方法,以创建、操纵和分析脂质及生物膜。这些包括使用化学和化学酶法从头合成脂质和膜、利用光遗传学和蛋白质工程编辑预先存在的膜、使用生物正交化学检测脂质代谢和转运,以及探究脂质 - 蛋白质相互作用和膜生物物理性质。由此呈现出一个新兴领域的图景,化学家、生物学家、物理学家和工程师在其中紧密合作——就像脂质本身一样——以更清晰地描述脂质和膜的性质、行为及功能。