德国慕尼黑工业大学Boekhoven, Job报道了化学驱动的动态组合库中基于模板的复制。相关研究成果发表在2024年7月16日出版的《自然—化学》。

科学面临的最大挑战之一是确定生命如何从分子混合物中自发出现。一个复杂的因素是，生命及其分子本质上是不稳定的——RNA和蛋白质容易水解和变性。为了从头合成生命或更好地了解其起源，需要对不稳定分子进行选择机制。

该文中，研究人员提出了一个化学燃料驱动的动态组合文库，用于模拟RNA低聚和去低聚，并在动力学控制下为选择和纯化机制提供了新的思路。在实验中，低聚物只能通过连续生产来维持。杂交是选择不稳定分子的有力工具，可提供低聚和反低聚速率的反馈。此外，研究发现温度法可用于纯化低聚物文库。此外，模板辅助的基于凝聚层的原细胞内低聚体的形成改变了其隔腔的物理性质，例如它们的融合能力。低聚物生产和物理性能之间的这种相互耦合是实现合成寿命的关键一步。

附：英文原文

Title: Template-based copying in chemically fuelled dynamic combinatorial libraries

Author: Kriebisch, Christine M. E., Burger, Ludwig, Zozulia, Oleksii, Stasi, Michele, Floroni, Alexander, Braun, Dieter, Gerland, Ulrich, Boekhoven, Job

Issue&Volume: 2024-07-16

Abstract: One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture of molecules. A complicating factor is that life and its molecules are inherently unstable—RNA and proteins are prone to hydrolysis and denaturation. For the de novo synthesis of life or to better understand its emergence at its origin, selection mechanisms are needed for unstable molecules. Here we present a chemically fuelled dynamic combinatorial library to model RNA oligomerization and deoligomerization and shine new light on selection and purification mechanisms under kinetic control. In the experiments, oligomers can only be sustained by continuous production. Hybridization is a powerful tool for selecting unstable molecules, offering feedback on oligomerization and deoligomerization rates. Moreover, we find that templation can be used to purify libraries of oligomers. In addition, template-assisted formation of oligomers within coacervate-based protocells changes its compartment’s physical properties, such as their ability to fuse. Such reciprocal coupling between oligomer production and physical properties is a key step towards synthetic life.

DOI: 10.1038/s41557-024-01570-5

Source: https://www.nature.com/articles/s41557-024-01570-5