A Chemical Model for the Prebiotic Origins of Tetrapyrrole Macrocycles

生命是如何在地球上起源的问题是科学界最具挑战性和最令人困惑的问题之一。这项由生命过程化学计划支持的项目将研究简单的、看似合理的益生化学反应，这些化学反应导致从早期地球可用的物质到四聚吡咯大循环。当今所有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。虽然对现代生物合成途径的模仿是有吸引力的，但这一提议撒下了一张大网，以检查各种反应，这些反应似乎可以导致四吡咯大环的形成，包括那些当今生物化学的反应，以及那些具有类似性质的类似物，这些类似物可能在益生化学中发挥核心作用。这里的一个论点是，可能有不同的途径可以到达关键的四吡咯大环，包括现在的现代途径，它们在益生元时代是有效的。还将研究随后转换四吡咯大环并改变其性质的简单化学反应，如在导致血红素和叶绿素的生物合成途径中发生的反应。这个项目的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源利用系统出现的关键里程碑，对光合作用来说似乎是必不可少的，这不仅可能是生命起源的核心，还可能增强我们对地球转型最早步骤的理解。也许最重要的是对参与这个项目的学生的教育和培训，以及由PI教授的一门相关课程--《生命的分子起源》，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.