近日，英国伦敦帝国理工学院Thomas E. Ouldridge团队研究了无酶催化模板DNA二聚化的信息传播与弱产物抑制。2025年6月5日，《自然-化学》杂志发表了这一成果。

通过序列特异性、模板催化的分子组装进行信息传播是促进生命生化复杂性的关键过程，仅从20个不同的构建块中产生数千种序列定义的蛋白质。然而，在非生物环境中，特别是在无酶环境中，催化模板的利用很少见，因为即使是模板催化的二聚体形成也具有挑战性。通常，产物抑制——产物比单个单体更强烈地结合模板的趋势——会阻止催化转化。

研究组提出了一种合理设计的无酶系统，其中DNA模板以微弱的产物抑制作用催化序列特异性DNA二聚体的产生。他们证明了九种不同二聚体的选择性模板化具有高特异性和催化周转性，然后证明了产物可以参与下游反应，最后证明了二聚可以与共价键形成偶联。最重要的是，该机制展示了构建合成分子模板系统的设计原理，这是将这一强大的基序应用于非生物环境以从少量构建块构建许多复杂分子和材料的第一步。

附：英文原文

Title: Information propagation through enzyme-free catalytic templating of DNA dimerization with weak product inhibition

Author: Cabello-Garcia, Javier, Mukherjee, Rakesh, Bae, Wooli, Stan, Guy-Bart V., Ouldridge, Thomas E.

Issue&Volume: 2025-06-05

Abstract: Information propagation by sequence-specific, template-catalysed molecular assembly is a key process facilitating life’s biochemical complexity, yielding thousands of sequence-defined proteins from only 20 distinct building blocks. However, exploitation of catalytic templating is rare in non-biological contexts, particularly in enzyme-free environments, where even the template-catalysed formation of dimers is challenging. Typically, product inhibition—the tendency of products to bind to templates more strongly than individual monomers—prevents catalytic turnover. Here we present a rationally designed enzyme-free system in which a DNA template catalyses, with weak product inhibition, the production of sequence-specific DNA dimers. We demonstrate selective templating of nine different dimers with high specificity and catalytic turnover, then we show that the products can participate in downstream reactions, and finally that the dimerization can be coupled to covalent bond formation. Most importantly, our mechanism demonstrates a design principle for constructing synthetic molecular templating systems, a first step towards applying this powerful motif in non-biological contexts to construct many complex molecules and materials from a small number of building blocks.

DOI: 10.1038/s41557-025-01831-x

Source: https://www.nature.com/articles/s41557-025-01831-x