Modern diversification of the amino acid repertoire driven by oxygen
Matthias Granold, Parvana Hajieva, Monica Ioana Toşa, Florin-Dan Irimie and Bernd Moosmann
PNAS 2018 January, 115 (1) 41-46. https://doi.org/10.1073/pnas.1717100115
Edited by Harry B. Gray, California Institute of Technology, Pasadena, CA, and approved November 21, 2017 (received for review October 1, 2017)
Significance
All life uses the same 20 amino acids, but only 7–13 early amino acids seem to be indispensable to build functional proteins. Thus, what triggered the introduction of the additional amino acids? Employing quantum chemical calculations and biochemical experiments, we find that the additional amino acids have become systematically “softer” (Ralph G. Pearson) over time, more redox-reactive, and more capable of protecting cells from destruction by oxygen free radicals. Hence, it appears that molecular oxygen forced life to incorporate novel amino acids with augmented redox properties into the genetic code. The present study provides a plausible scenario for a more than 80-y-old problem of fundamental biochemistry: Why these 20 amino acids?
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.
amino acidsgenetic codemolecular oxygenorigin of liferedox reactivity
Footnotes
↵1To whom correspondence should be addressed. Email: moosmann@uni-mainz.de.
Author contributions: M.G. and B.M. conceptualized the project; M.G., P.H., M.I.T., F. -D. I., and B.M. designed research; M.G., P.H., M.I.T., F. -D. I., and B.M. performed research; M.G., P.H., M.I.T., F. -D. I., and B.M. analyzed data; and B.M. wrote the paper.
Conflict of interest statement: Some of the chemical compounds used in this work have been patented by the Max Planck Society, naming author B.M. as one of the inventors (EP 1113795 B1).
This article is a PNAS Direct Submission.
This article contains supporting information online at
Published under the PNAS license.
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