Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, University of Strasbourg, 8 Allée Gaspard Monge, 67000 Strasbourg, France.
J Am Chem Soc. 2023 Nov 29;145(47):25614-25620. doi: 10.1021/jacs.3c07319. Epub 2023 Nov 16.
Phospholipids are the primary constituents of cell membranes across all domains of life, but how and when phospholipids appeared on early Earth remains unknown. Pressingly, most prebiotic syntheses of complex phospholipids rely upon substrates not yet shown to have been available on early Earth. Here, we describe potentially prebiotic syntheses of a diverse array of complex phospholipids and their building blocks. First, we show that choline could have been produced on early Earth by stepwise -methylation of ethanolamine. Second, taking a systems chemistry approach, we demonstrate that the intrinsically activated glycerol-2,3-cyclic phosphate undergoes ring opening with combinations of prebiotic amino alcohols to yield complex phospholipid headgroups. Importantly, this pathway selects for the formation of 2-amino alcohol-bearing phospholipid headgroups and enables the accumulation of their natural regioisomers. Finally, we show that the dry-state ring opening of cyclic lysophosphatidic acids leads to a range of self-assembling lysophospholipids. Our results provide new prebiotic routes to key intermediates on the way toward modern phospholipids and illuminate the potential origin and evolution of cell membranes.
磷脂是所有生命领域细胞膜的主要组成部分，但磷脂是如何以及何时出现在早期地球上的仍然未知。紧迫的是，大多数复杂磷脂的前生物合成依赖于尚未证明在早期地球上存在的底物。在这里，我们描述了一系列复杂磷脂及其构建块的潜在前生物合成方法。首先，我们表明，通过乙醇胺的逐步 -甲基化，胆碱可能已经在早期地球上产生。其次，采用系统化学方法，我们证明了内在激活的甘油-2,3-环磷酸酯与前生物氨基酸醇的组合发生开环反应，生成复杂的磷脂头部基团。重要的是，该途径选择形成带有 2-氨基醇的磷脂头部基团，并能够积累它们的天然非对映异构体。最后，我们表明，环状溶血磷脂酸的干态开环导致一系列自组装溶血磷脂的形成。我们的结果为现代磷脂形成过程中的关键中间体提供了新的前生物途径，并阐明了细胞膜的潜在起源和进化。
