A Chemical Model for the Prebiotic Origins of Tetrapyrrole Macrocycles

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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.