The Future of Prebiotic Chemistry
Two recent papers reporting advances in our understanding of how a protometabolism may have developed in a prebiotic world add new meaning to the theme “First Reactions” and highlight the challenges facing synthetic organic chemists attempting to retrodict the origins of life.
Alexander J. Wagner and Donna G. Blackmond*
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States
ACS Cent. Sci., 2016, 2 (11), pp 775–777
Publication Date (Web): November 11, 2016
Copyright © 2016 American Chemical Society
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Source/Fonte: Lawrence Livermore National Laboratory
Here is a puzzle: in what area of organic synthesis research are synthetic organic chemists a minority? According to Albert Eschenmoser,(1) it is in the field of prebiotic chemistry: the study of the reactions and molecules that led to the emergence of life on earth. Biologists, mathematicians, and astronomers have traditionally weighed in on this problem proportionally more than organic chemists. When chemists do play in this field, they are venerable—Albert Eschenmoser, Leslie Orgel, Jack Szostak, and Ronald Breslow, to name a few—but only rarely has the field been the province of early career organic chemists. It may be that the challenge of finding funding for such an esoteric problem comes easier to established scientists in a world increasingly focused on practical applications. But a desire to explore this field also speaks to the uniquely reflective mindset required to contemplate the greatest retrosynthetic analysis of all, leading us from modern enzymes and genetic polymers back to the etiology of biomolecules. A glimpse into this kind of thinking is provided in a recent Nature Chemistry paper(2) by Adam J. Coggins and Matthew W. Powner, along with a 2015 Nature Chemistry paper(3) by John D. Sutherland and co-workers.
A uniquely reflective mindset is required to contemplate the greatest retrosynthetic analysis of all, leading us from modern enzymes and genetic polymers back to the etiology of biomolecules.
Probing plausible prebiotic chemistry requires an extraordinary combination of outlook and expertise that differs subtly from that employed in other areas of organic synthesis. For example, rather than seeking to develop novel synthetic methodologies and complex molecular architectures, origin-of-life researchers must look to unlock the secrets of ancient and simple processes that might have been available to construct the building blocks of life in a primordial world. The principal authors of these two Nature Chemistry papers, Powner and Sutherland, also authored (along with Beatrice Gerland) the breakthrough 2009 Nature paper(4) demonstrating a prebiotically plausible route to activated pyrimidine ribonucleotides, thus solving a long-standing conundrum of the “RNA World” hypothesis.(5) That work comprised Powner’s PhD studies with Sutherland, who, largely inspired by Eschenmoser and unusually for this field, has from the start dedicated his career to synthetic prebiotic chemistry. Powner seems set to do the same.
The “vestiges of an earlier reactivity” point to α-phosphorylation instead of terminal phosphorylation in the glycolytic and other protometabolic pathways.
The 2016 Powner work tackles the problem of how metabolism could have evolved from reactions of simple organic molecules prior to the emergence of complex enzymatic processes. The focus is on glycolysis with an emphasis directed toward the synthesis of phosphoenol pyruvate (1): a high-energy, versatile, and ubiquitous molecule in modern metabolism (1 in Scheme 1). Nailing down a plausible nonenzymatic synthetic route to this key intermediate would be an important step in unwinding protometabolic pathways.
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