The transition from unregulated, prebiotic chemistry to metabolic-like systems capable of supporting an evolving protocell has remained difficult to explain. One hypothesis is that early catalysts began to prune the chemical landscape in a manner that facilitated the emergence of modern-day enzymes. As enzymes frequently rely on the intrinsic reactivity of metal ions, it follows that these early catalysts may have been metal ions coordinated to prebiotic peptides that have remained as core structures within extant proteins. Here, we demonstrate that UV light directly selects for the types of metal-binding peptide motifs found in biology. This is because bare cysteine is much more susceptible to photolysis than cysteine bound by a metal ion. Therefore, peptides with greater affinity for environmentally available metal ions, such as Fe2+ or Zn2+, are more stable. Our results are supported by mass spectrometry, calorimetry, X-ray absorption, NMR spectroscopy, transient absorption pump probe spectroscopy, and excited-state quantum-chemical calculations. Photostability arises from the ability of the metal ion to engage transiently generated reactive radical centers in a manner that prevents subsequent degradative processes. The data are consistent with the enrichment of a restricted set of high affinity, extant-like metallopeptides in surficial environments on the early Earth.

ALBA Synchrotron Carrer Llum 2 26 Cerdanyola del Valles Barcelona 08290 Spain

Department of Astronomy Harvard University 60 Garden Street Cambridge Massachusetts 02138 USA

Department of Chemistry University of Alberta Edmonton Alberta T6G 2G2 Canada

Department of Physics Faculty of Science University of Ostrava 30 dubna 22 701 03 Ostrava Czech Republic

Department of Physics University of Trento 38123 Povo Italy

DiCIBIO University of Trento 38123 Povo Italy

Institute of Advanced Materials Faculty of Chemistry Wrocław University of Science and Technology Wrocław Poland

Laboratory of Bio Inorganic Chemistry Department of Pharmacy and Biotechnology University of Bologna Bologna Italy

Magnetic Resonance Centre Department of Chemistry Ugo Schiff University of Florence Sesto Fiorentino Italy

Zobrazit více v PubMed

Copley S. D. Smith E. Morowitz H. J. Bioorg. Chem. 2007;35:430–443. doi: 10.1016/j.bioorg.2007.08.001. PubMed DOI

Muchowska K. B. Varma S. J. Moran J. Nature. 2019;569:104–107. doi: 10.1038/s41586-019-1151-1. PubMed DOI PMC

Keller M. A. Turchyn A. V. Ralser M. Mol. Syst. Biol. 2014;10:725. doi: 10.1002/msb.20145228. PubMed DOI PMC

Bonfio C. Godino E. Corsini M. Fabrizi de Biani F. Guella G. Mansy S. S. Nat. Catal. 2018;1:616–623. doi: 10.1038/s41929-018-0116-3. DOI

Walton C. R. Rimmer P. Shorttle O. Front. Earth Sci. 2022;10:1011717. doi: 10.3389/feart.2022.1011717. DOI

Patel B. H. Percivalle C. Ritson D. J. Duffy C. D. Sutherland J. D. Nat. Chem. 2015;7:301–307. doi: 10.1038/nchem.2202. PubMed DOI PMC

Kim H.-J. Benner S. A. Proc. Natl. Acad. Sci. U. S. A. 2017;114:11315–11320. doi: 10.1073/pnas.1710778114. PubMed DOI PMC

Cohen Z. R. Kessenich B. L. Hazra A. Nguyen J. Johnson R. S. MacCoss M. J. Lalic G. Black R. A. Keller S. L. ChemBioChem. 2022;23:e202100614. doi: 10.1002/cbic.202100614. PubMed DOI PMC

Toner J. D. Catling D. C. Proc. Natl. Acad. Sci. U. S. A. 2020;117:883–888. doi: 10.1073/pnas.1916109117. PubMed DOI PMC

Tutolo B. M. Perrin R. Lauer R. Bossaer S. Tosca N. J. Hutchings A. Sevgen S. Nightingale M. Ilg D. Mott E. B. Wilson T. Life. 2024;14:1624. doi: 10.3390/life14121624. PubMed DOI PMC

Deamer D. Weber A. L. Cold Spring Harb. Perspect. Biol. 2010;2:a004929. PubMed PMC

Becker S. Feldmann J. Wiedemann S. Okamura H. Schneider C. Iwan K. Crisp A. Rossa M. Amatov T. Carell T. Science. 2019;366:76–82. doi: 10.1126/science.aax2747. PubMed DOI

Green N. J. Xu J. Sutherland J. D. J. Am. Chem. Soc. 2021;143:7219–7236. doi: 10.1021/jacs.1c01839. PubMed DOI PMC

Szabla R., in Prebiotic Photochemistry: From Urey–Miller-like Experiments to Recent Findings, ed. F. Saija and G. Cassone, The Royal Society of Chemistry, 2021, pp. 79–106

Rapf R. J. Vaida V. Phys. Chem. Chem. Phys. 2016;18:20067–20084. doi: 10.1039/C6CP00980H. PubMed DOI

Xu J. Chmela V. Green N. J. Russell D. A. Janicki M. J. Góra R. W. Szabla R. Bond A. D. Sutherland J. D. Nature. 2020;582:60–66. doi: 10.1038/s41586-020-2330-9. PubMed DOI PMC

Xu J. Tsanakopoulou M. Magnani C. J. Szabla R. Šponer J. E. Šponer J. Góra R. W. Sutherland J. D. Nat. Chem. 2017;9:303–309. doi: 10.1038/nchem.2664. PubMed DOI PMC

Janicki M. J. Roberts S. J. Šponer J. Powner M. W. Góra R. W. Szabla R. Chem. Commun. 2018;54:13407–13410. doi: 10.1039/C8CC07343K. PubMed DOI

Todd Z. R. Szabla R. Szostak J. W. Sasselov D. D. Chem. Commun. 2019;55:10388–10391. doi: 10.1039/C9CC05265H. PubMed DOI PMC

Bertram L. Roberts S. J. Powner M. W. Szabla R. Phys. Chem. Chem. Phys. 2022;24:21406–21416. doi: 10.1039/D2CP03167A. PubMed DOI PMC

Serrano-Andrés L. Merchán M. J. Photochem. Photobiol., C. 2009;10:21–32. doi: 10.1016/j.jphotochemrev.2008.12.001. DOI

Beckstead A. A. Zhang Y. de Vries M. S. Kohler B. Phys. Chem. Chem. Phys. 2016;18:24228–24238. doi: 10.1039/C6CP04230A. PubMed DOI

Ranjan S. Sasselov D. D. Astrobiology. 2017;17:169–204. doi: 10.1089/ast.2016.1519. PubMed DOI

Ranjan S. Kufner C. L. Lozano G. G. Todd Z. R. Haseki A. Sasselov D. D. Astrobiology. 2022;22:242–262. PubMed PMC

Todd Z. R. Lozano G. G. Kufner C. L. Ranjan S. Catling D. C. Sasselov D. D. Astrobiology. 2024;24:559–569. doi: 10.1089/ast.2023.0077. PubMed DOI

Rimmer P. B. Thompson S. J. Xu J. Russell D. A. Green N. J. Ritson D. J. Sutherland J. D. Queloz D. P. Astrobiology. 2021;21:1099–1120. doi: 10.1089/ast.2020.2335. PubMed DOI PMC

Madsen M. M. Jensen F. Thøgersen J. Phys. Chem. Chem. Phys. 2020;22:2307–2318. doi: 10.1039/C9CP05836B. PubMed DOI

Thøgersen J. Chatterley A. S. Weidner T. Jensen F. J. Am. Chem. Soc. 2023;145:9777–9785. doi: 10.1021/jacs.3c01469. PubMed DOI

Foden C. S. Islam S. Fernández-García C. Maugeri L. Sheppard T. D. Powner M. W. Science. 2020;370:865–869. doi: 10.1126/science.abd5680. PubMed DOI

Wehbi S. Wheeler A. Morel B. Manepalli N. Minh B. Q. Lauretta D. S. Masel J. Proc. Natl. Acad. Sci. U. S. A. 2024;121:e2410311121. doi: 10.1073/pnas.2410311121. PubMed DOI PMC

Belmonte L. Mansy S. S. J. Chem. Inf. Model. 2017;57:3162–3171. doi: 10.1021/acs.jcim.7b00468. PubMed DOI

Rossetto D. Valer L. Yeh Martín N. Guella G. Hongo Y. Mansy S. S. ACS Earth Space Chem. 2022;6(5):1221–1226. doi: 10.1021/acsearthspacechem.2c00042. PubMed DOI PMC

Bonfio C. Valer L. Scintilla S. Shah S. Evans D. J. Jin L. Szostak J. W. Sasselov D. D. Sutherland J. D. Mansy S. S. Nat. Chem. 2017;9:1229–1234. doi: 10.1038/nchem.2817. PubMed DOI PMC

Scintilla S. Rossetto D. Clémancey M. Rendon J. Ranieri A. Guella G. Assfalg M. Borsari M. Gambarelli S. Blondin G. Mansy S. S. Chem. Sci. 2025;16:4614–4624. doi: 10.1039/D5SC00524H. PubMed DOI PMC

Aithal A. Dagar S. Rajamani S. ACS Omega. 2023;8:5197–5208. doi: 10.1021/acsomega.2c07635. PubMed DOI PMC

Ranjan S. Wordsworth R. Sasselov D. D. Astrophys. J. 2017;843:110. doi: 10.3847/1538-4357/aa773e. DOI

Hazen R. M. Am. J. Sci. 2013;313:807–843. doi: 10.2475/09.2013.01. DOI

Belmonte L. Rossetto D. Forlin M. Scintilla S. Bonfio C. Mansy S. S. Phys. Chem. Chem. Phys. 2016;18:20104–20108. doi: 10.1039/C6CP00608F. PubMed DOI

Valer L. Rossetto D. Parkkila T. Sebastianelli L. Guella G. Hendricks A. L. Cowan J. A. Sang L. Mansy S. S. ChemBioChem. 2022;23:e202200202. doi: 10.1002/cbic.202200202. PubMed DOI PMC

Kochańczyk T. Jakimowicz P. Krężel A. Chem. Comm. 2013;49:1312–1314. doi: 10.1039/C2CC38174E. PubMed DOI

Software for Science Developments (S4SD), 2023, http://www.affinimeter.com

Clark-Baldwin K. Tierney D. L. Govindaswamy N. Gruff E. S. Kim C. Berg J. Koch S. A. Penner-Hahn J. E. J. Am. Chem. Soc. 1998;120:8401–8409. doi: 10.1021/ja980580o. DOI

Kelly R. A. Andrews J. C. DeWitt J. G. Microchem. J. 2002;71:231–245. doi: 10.1016/S0026-265X(02)00015-2. DOI

Dreuw A. Wormit M. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2015;5:82–95.

Karbalaei Khani S. Marefat Khah A. Hättig C. Phys. Chem. Chem. Phys. 2018;20:16354–16363. doi: 10.1039/C8CP00643A. PubMed DOI

Hättig C., in Adv. Quantum Chem., ed. H. J. Å. Jensen, Academic Press, 2005, vol. 50, pp. 37–60

Laitaoja M. Valjakka J. Jänis J. Inorg. Chem. 2013;52:10983–10991. doi: 10.1021/ic401072d. PubMed DOI

Sarkar S. Dagar S. Rajamani S. ChemSystemsChem. 2021;3:e2100014. doi: 10.1002/syst.202100014. DOI

Rajamani S. Vlassov A. Benner S. Coombs A. Olasagasti F. Deamer D. Origins Life Evol. B. 2008;38:57–74. doi: 10.1007/s11084-007-9113-2. PubMed DOI

Rossetto D. Sebastianelli L. Oberegger S. Todorovic S. Haas H. Mansy S. S. Adv. Biol. 2024;8:e2300545. doi: 10.1002/adbi.202300545. PubMed DOI

Rossetto D. Cvjetan N. Walde P. Mansy S. S. Acc. Chem. Res. 2024;57:2293–2302. doi: 10.1021/acs.accounts.4c00254. PubMed DOI PMC

Merritt H. I. Sawyer N. Arora P. S. Pept. Sci. 2020;112:e24145. doi: 10.1002/pep2.24145. PubMed DOI PMC

Fu M. Blackshear P. J. Genome Res. 2017;17:130–143. PubMed PMC

Friesen W. J. Darby M. K. J. Biol. Chem. 2001;276:1968–1973. doi: 10.1074/jbc.M008927200. PubMed DOI

Zerkle A. L. House C. H. Brantley S. L. Am. J. Sci. 2005;305:467–502. doi: 10.2475/ajs.305.6-8.467. DOI

Isalan M., in Encyclopedia of Biological Chemistry, ed. W. J. Lennarz and M. D. Lane, Academic Press, Waltham, 2nd edn, 2013, pp. 575–579

Rodríguez J. Mosquera J. Vázquez O. Vázquez M. E. Mascareñas J. L. Chem. Commun. 2014;50:2258–2260. doi: 10.1039/C3CC47599A. PubMed DOI

Alva V. Lupas A. N. Curr. Opin. Struct. Biol. 2018;48:103–109. doi: 10.1016/j.sbi.2017.11.006. PubMed DOI

Pace N. J. Weerapana E. Biomolecules. 2014;4:419–434. doi: 10.3390/biom4020419. PubMed DOI PMC

Lauber N. Flamm C. Ruiz-Mirazo K. BioEssays. 2021;43:1–12. doi: 10.1002/bies.202100103. PubMed DOI