Non-enzymatic Analogues of Amino Acid Biosynthesis to Understand the Origin of Life

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Amino acids are the major constituents of enzymes – which in turn are required by organisms to catalyze the synthesis of amino acids! How did this chicken-and-egg situation begin? Chemists have developed a multitude of routes to synthesize amino acids, but biochemical amino acid synthesis proceeds from keto acids via a rather unusual detour: Nitrogen, in the form of ammonia, is used to synthesize glutamate from α-ketoglutarate. Glutamate subsequently undergoes transamination reactions to synthesize all other proteinogenic amino acids or their precursors. But how were amino acids synthesized in a pre-enzymatic world and is there a relation to today’s biochemistry? One popular concept suggests that the enzymatic pathways known today originated from reaction networks consisting of simple organic molecules using naturally occurring metals or minerals as catalysts. In support of this idea, prebiotic analogues of the Krebs cycle or acetyl CoA pathway have recently been identified in the supervisor’s lab, among others. However, a prebiotic reaction network that mimics biochemical amino acid synthesis remains elusive. The aim of this project is to investigate the prebiotic origins of amino acid biosynthesis. Initial mechanistic and kinetic studies will thus set the basis for a systematic study of catalytic reaction networks for amino acid synthesis.