Non-enzymatic Analogues of Amino Acid Biosynthesis to Understand the Origin of Life

氨基酸生物合成的非酶类似物了解生命的起源

• 批准号: 463262726
• 负责人: Dr. Robert Mayer
• 金额: --
• 依托单位: Lehrstuhl für Organische Chemie I
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/463262726?language=en
• 关键词: Non; enzymatic; Analogues; Amino; Acid

Amino acids are the major constituents of enzymes – which in turn are required by organisms to catalyze the synthesis of amino acids! How did this chicken-and-egg situation begin? Chemists have developed a multitude of routes to synthesize amino acids, but biochemical amino acid synthesis proceeds from keto acids via a rather unusual detour: Nitrogen, in the form of ammonia, is used to synthesize glutamate from α-ketoglutarate. Glutamate subsequently undergoes transamination reactions to synthesize all other proteinogenic amino acids or their precursors. But how were amino acids synthesized in a pre-enzymatic world and is there a relation to today’s biochemistry? One popular concept suggests that the enzymatic pathways known today originated from reaction networks consisting of simple organic molecules using naturally occurring metals or minerals as catalysts. In support of this idea, prebiotic analogues of the Krebs cycle or acetyl CoA pathway have recently been identified in the supervisor’s lab, among others. However, a prebiotic reaction network that mimics biochemical amino acid synthesis remains elusive. The aim of this project is to investigate the prebiotic origins of amino acid biosynthesis. Initial mechanistic and kinetic studies will thus set the basis for a systematic study of catalytic reaction networks for amino acid synthesis.

氨基酸是酶的主要成分，而酶又是生物体催化氨基酸合成所必需的！这种鸡生蛋还是蛋生鸡的局面是如何开始的？化学家们已经开发出多种合成氨基酸的途径，但生化氨基酸合成是通过一个相当不寻常的弯路从酮酸开始的：氮以氨的形式被用来从α-酮戊二酸合成谷氨酸。谷氨酸随后经历转氨反应以合成所有其他蛋白质氨基酸或其前体。但是，在前酶的世界中，氨基酸是如何合成的？这与今天的生物化学有关系吗？一个流行的概念认为，今天已知的酶途径起源于由简单的有机分子组成的反应网络，使用天然存在的金属或矿物质作为催化剂。为了支持这一想法，克雷布斯循环或乙酰辅酶A途径的益生元类似物最近在主管的实验室中被鉴定出来。然而，模仿生化氨基酸合成的益生元反应网络仍然难以捉摸。本项目的目的是研究氨基酸生物合成的益生元起源。因此，初步的机理和动力学研究将为氨基酸合成催化反应网络的系统研究奠定基础。