A Chemical Model for the Prebiotic Origins of Tetrapyrrole Macrocycles

生命如何在地球上起源的问题是科学中最具挑战性和最令人困惑的问题之一。这个由生命过程化学计划支持的项目将检验从早期地球可利用物质到四吡咯大环的简单、似是而非的生命前化学反应。所有现今的生物体都使用一种单一的、通用的途径来构建四吡咯分子。虽然现代生物合成途径的模仿很有吸引力，但这一建议广泛地研究了可能导致四吡啶大环形成的各种反应，包括当今生物化学的反应，以及具有相似性质的类似物，这些类似物可能在益生元化学中发挥核心作用。这里的一个论点是，可能有多种途径进入关键的四吡咯大环，包括现在的现代途径，这些途径在益生元时代起作用。随后转化四吡咯大环并改变其性质的简单化学反应，如发生在导致血红素和叶绿素的生物合成途径中，也将进行研究。这个项目更广泛的影响包括加深我们对生物发生和能量代谢在自我复制系统起源中的作用的理解。阐明包括光合作用在内的能量利用系统出现的关键里程碑，对于光合作用来说，四吡咯大循环似乎是必不可少的，这不仅是生命起源的核心，而且可能增加我们对地球转变最早步骤的理解。也许最重要的是对参与该项目的学生的教育和培训，以及PI将教授的一门名为“生命的分子起源”的相关课程，这两门课程都有望激发年轻科学家的好奇心，加深他们对科学的热情。

The question of how life originated on Earth is one of the most challenging and perplexing problems in science. This project supported by the Chemistry of Life Processes Program will examine simple, plausibly prebiotic chemical reactions that lead from early-Earth available substances to tetrapyrrole macrocycles. All present-day living organisms use a single, universal pathway for the construction of tetrapyrrole molecules. While mimicry of the modern biosynthetic pathway is attractive, this proposal casts a broad net to examine diverse reactions that plausibly can lead to the formation of tetrapyrrole macrocycles, including those of present-day biochemistry as well as analogues with similar properties that could have played a central role in prebiotic chemistry. A thesis here is that there may have been diverse pathways to the critical class of tetrapyrrole macrocycles, including the now modern pathway, which were operative in the prebiotic era. Simple chemical reactions that subsequently transform tetrapyrrole macrocycles and alter their properties, as occurs in the biosynthetic pathways leading to heme and chlorophylls, also will be examined. The broader impacts of this project include deepening our understanding of biogenesis and the role of energy metabolism in the origin of a self-replicating system. Elucidation of critical milestones for the emergence of energy-utilizing systems including photosynthesis, for which tetrapyrrole macrocycles would seem essential, may not only be central to life's origins but may also augment our understanding of the earliest steps in the transformation of the Earth. Perhaps most important is the education and training of students who work on this project, and a related course to be taught by the PI entitled "The Molecular Origins of Life", both of which are expected to spark young scientists' curiosity and deepen their passion for science.