Transformations within the TCA cycle enable the net oxidation of an acetyl group into two molecules of carbon dioxide. This metabolic pathway serves critical roles in the storage of chemical potential within biological cofactors, as well as provides building blocks (including amino acids) for biopolymer synthesis. Genomic and metabolic analyses suggest that parts of the TCA cycle may have been active at the origins of metabolism, likely in an anabolic capacity. However, the reactions proceed poorly, or not at all, without complex catalysts and biological cofactors. Simpler uncatalyzed analogs of the TCA cycle, with more limited functionality, may have emerged under prebiotic conditions and laid the foundation for the development of an increasingly sophisticated metabolism. In work described here, an aldol addition of glyoxylate to pyruvate (or oxaloacetate) initiates a series of proto-metabolic reactions that recapitulate significant portions of the citric acid cycle. The reactions proceed under aqueous conditions at mild temperature and without catalysts or cofactors. The pathway may have served as a source of monomeric building blocks for early peptides, depsipeptides, and nucleic acids.

Glyoxylate-based protometabolism serves as an analog of the citric acid cycle

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.