The evolution of complex chemical inventory from Darwin’s nutrient-rich warm pond necessitated rudimentary yet efficient catalytic folds. Short peptides and their self-organized microstructures, ranging from spherical colloids to amyloidogenic aggregates might have played a crucial role in the emergence of contemporary catalytic entities. However, the question of how short peptide fragments had functions akin to contemporary complex enzymes to catalyze cleavage and formation of highly stable peptide bonds that constitute the backbone of all proteins remains an unresolved yet fundamentally important question in terms of the origins of enzymes. We report short-peptide-based spherical assemblies that demonstrated residue-specific cleavage and formation of peptide bonds of diverse peptide-based substrates under aqueous environment. Despite the short sequence length, the assemblies utilized the synergistic collaboration of four residues which included the catalytic triad of extant serine proteases with a nonproteinogenic amino acid (quinone moiety), to facilitate proteolysis, ligation, and a three-step (hydrolysis–ligation–hydrolysis) cascade. Such short-peptide-based catalytic assemblies argue for their candidacy as the earliest protein folds and open up avenues for biotechnological applications.

中文翻译：

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通过基于短肽的组装体在水中进行位点选择性肽键水解和连接


达尔文营养丰富的温暖池塘中复杂化学物质的演变需要基本但有效的催化折叠。短肽及其自组织微观结构，从球形胶体到淀粉样蛋白聚集体，可能在当代催化实体的出现中发挥了至关重要的作用。然而，就酶的起源而言，短肽片段如何具有类似于当代复杂酶的功能来催化裂解和形成高度稳定的肽键（构成所有蛋白质的主链）仍然是一个尚未解决但至关重要的问题。我们报告了基于短肽的球形组件，该组件证明了在水性环境下不同基于肽的底物的残基特异性裂解和肽键的形成。尽管序列长度较短，但组装体利用了四个残基的协同协作，其中包括现有丝氨酸蛋白酶的催化三联体与非蛋白原氨基酸（醌部分），以促进蛋白水解、连接和三步（水解-连接-水解）级联。这种基于短肽的催化组装体有资格成为最早的蛋白质折叠并为生物技术应用开辟途径。