The Origin of Metabolism and Heredity

Lead Research Organisation: University College London
Department Name: Genetics Evolution and Environment

Abstract

An autotrophic origin for life is increasingly gaining experimental plausibility. Nonenzymatic equivalents already exist for core parts of metabolism conserved in all life, including glycolysis, gluconeogenesis, Krebs and glyoxylate cycles. Such biomimetic pathways are not available for purines and related cofactors, despite evidence to suggest their importance in growing protocells and at the origin of genetic information. Similarly, the compatibility of polymerisation of nucleotides and an autotrophic origin has not yet been experimentally demonstrated. Previous investigations into the purine de novo synthesis pathway have not yet yielded fruitful results in aqueous solvents; however, with the use of HPLC-MS, the identification of unstable intermediates and those without chemical standards may now be feasible. The biomimetic synthesis of the cofactors, pyridoxal and NMN, would experimentally link the production of amino acids to Krebs cycle intermediates: these cofactors may also be necessary for the formation of purines. Polymerisation of RNA nucleotides using amino acid and short peptide cofactors would be the first step in the development of genetic information capable of exploiting a chemical network out of equilibrium. Investigation into the chemical conditions in which these reactions are possible utilises a variety of methods including HPLC-MS, GC-MS, NMR spectroscopy and IR spectroscopy.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
NE/S007229/1 30/09/2019 29/09/2027
2843342 Studentship NE/S007229/1 30/09/2023 23/09/2027 William Webb