Modern diversification of the amino acid repertoire driven by oxygen

Abstract

All extant life employs the same 20 amino acids for protein biosynthesis. Studies on the number of amino acids necessary to produce a foldable and catalytically active polypeptide have shown that a basis set of 7–13 amino acids is sufficient to build major structural elements of modern proteins. Hence, the reasons for the evolutionary selection of the current 20 amino acids out of a much larger available pool have remained elusive. Here, we have analyzed the quantum chemistry of all proteinogenic and various prebiotic amino acids. We find that the energetic HOMO–LUMO gap, a correlate of chemical reactivity, becomes incrementally closer in modern amino acids, reaching the level of specialized redox cofactors in the late amino acids tryptophan and selenocysteine. We show that the arising prediction of a higher reactivity of the more recently added amino acids is correct as regards various free radicals, particularly oxygen-derived peroxyl radicals. Moreover, we demonstrate an immediate survival benefit conferred by the enhanced redox reactivity of the modern amino acids tyrosine and tryptophan in oxidatively stressed cells. Our data indicate that in demanding building blocks with more versatile redox chemistry, biospheric molecular oxygen triggered the selective fixation of the last amino acids in the genetic code. Thus, functional rather than structural amino acid properties were decisive during the finalization of the universal genetic code.