美国斯克利普斯研究所Blackmond, Donna G.团队报道了生命起源前连接反应中的对称破缺和手性扩增。相关研究成果于2024年2月28日发表在《自然》。

生物分子的单一手性是生命的标志。然而，合理化单一手性的产生方式仍然是一个具有挑战性的目标。目前研究通常集中在组成遗传聚合物RNA、DNA，以及肽的单体构建块（糖和氨基酸）的初始对称性破坏和随后的对映体富集上。然而，如果这些构建块仅部分对映体富集，则可能发生链生长停滞，在核酸的情况下，这被异想天开地称为“原始合成的问题”。

该文中，研究一种新的生命起源前合理的蛋白质生成肽途径时，发现该反应有利于异手性连接（即L单体与D单体的连接）。尽管这一发现似乎对于同源手性L-肽的生命起源前出现是个问题，但研究人员证明了这种异手性偏好为同源手性链中的对映体富集提供了一种机制。

在多组分竞争反应中，即使复杂混合物中只有一个分子表现出对映体浓度不平衡（非外消旋），所有反应物和产物也会发生对称性破坏、手性扩增和手性转移过程。溶解度的考虑使进一步的化学纯化和增强手性扩增合理化。实验数据和动力学模型支持，同源手性生物聚合物出现的这种生命起源前的合理机制。

附：英文原文

Title: Symmetry breaking and chiral amplification in prebiotic ligation reactions

Author: Deng, Min, Yu, Jinhan, Blackmond, Donna G.

Issue&Volume: 2024-02-28

Abstract: The single chirality of biological molecules is a signature of life. Yet, rationalizing how single chirality emerged remains a challenging goal1. Research has commonly focused on initial symmetry breaking and subsequent enantioenrichment of monomer building blocks—sugars and amino acids—that compose the genetic polymers RNA and DNA as well as peptides. If these building blocks are only partially enantioenriched, however, stalling of chain growth may occur, whimsically termed in the case of nucleic acids as “the problem of original syn”2. Here, in studying a new prebiotically plausible route to proteinogenic peptides3,4,5, we discovered that the reaction favours heterochiral ligation (that is, the ligation of L monomers with D monomers). Although this finding seems problematic for the prebiotic emergence of homochiral L-peptides, we demonstrate, paradoxically, that this heterochiral preference provides a mechanism for enantioenrichment in homochiral chains. Symmetry breaking, chiral amplification and chirality transfer processes occur for all reactants and products in multicomponent competitive reactions even when only one of the molecules in the complex mixture exhibits an imbalance in enantiomer concentrations (non-racemic). Solubility considerations rationalize further chemical purification and enhanced chiral amplification. Experimental data and kinetic modelling support this prebiotically plausible mechanism for the emergence of homochiral biological polymers.

DOI: 10.1038/s41586-024-07059-y

Source: https://www.nature.com/articles/s41586-024-07059-y