Iron–sulfur clusters are ancient cofactors that play a fundamental role in metabolism and may have impacted the prebiotic chemistry that led to life. However, it is unclear whether iron–sulfur clusters could have been synthesized on prebiotic Earth. Dissolved iron on early Earth was predominantly in the reduced ferrous state, but ferrous ions alone cannot form polynuclear iron–sulfur clusters. Similarly, free sulfide may not have been readily available. Here we show that UV light drives the synthesis of [2Fe–2S] and [4Fe–4S] clusters through the photooxidation of ferrous ions and the photolysis of organic thiols. Iron–sulfur clusters coordinate to and are stabilized by a wide range of cysteine-containing peptides and the assembly of iron–sulfur cluster-peptide complexes can take place within model protocells in a process that parallels extant pathways. Our experiments suggest that iron–sulfur clusters may have formed easily on early Earth, facilitating the emergence of an iron–sulfur-cluster-dependent metabolism.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Eck, R. V. & Dayhoff, M. O. Evolution of the structure of ferredoxin based on living relics of primitive amino acid sequences. Science 152, 363–366 (1966).
Goldford, J. E., Hartman, H., Smith, T. F. & Segrè, D. Remnants of an ancient metabolism without phosphate. Cell 168, 1126–1134 (2017).
Martin, W. & Russell, M. J. On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells. Phil. Trans. R. Soc. B 358, 59–85 (2003).
Martin, W. F., Sousa, F. L. & Lane, N. Energy at life's origin. Science 344, 1092–1093 (2014).
Maurel, M. & Leclerc, F. From foundation stones to life: concepts and results. Elements 12, 407–412 (2016).
Scintilla, S. et al. Duplications of an iron–sulphur tripeptide leads to the formation of a protoferredoxin. Chem. Commun. 52, 13456–13459 (2016).
Anbar, A. D. Elements and evolution. Science 322, 1481–1483 (2008).
Osterberg, R. Origins of metal ions in biology. Nature 249, 382–383 (1974).
Blöchl, E., Keller, M., Wachtershäuser, G. & Stetter, K. O. Reactions depending on iron sulfide and linking geochemistry with biochemistry. Proc. Natl Acad. Sci. USA 89, 8117–8120 (1992).
Cody, G. D. et al. Primordial carbonylated iron–sulfur compounds and the synthesis of pyruvate. Science 289, 1337–1340 (2000).
Ritson, D. & Sutherland, J. D. Prebiotic synthesis of simple sugars by photoredox systems chemistry. Nat. Chem. 4, 895–899 (2012).
Patel, B. H., Percivalle, C., Ritson, D. J., Duffy, C. D. & Sutherland, J. D. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. Nat. Chem. 7, 301–307 (2015).
Qi, W. et al. Glutathione complexed Fe–S centers. J. Am. Chem. Soc. 134, 10745–10748 (2012).
Fiser, B. et al. Glutathione as a prebiotic answer to α-peptide based life. J. Phys. Chem. B 119, 3940–3947 (2015).
Pandelia, M. E., Lanz, N. D., Booker, S. J. & Krebs, C. Mössbauer spectroscopy of Fe/S proteins. Biochim. Biophys. Acta 1853, 1395–1405 (2015).
Duin, E. C. et al. [2Fe-2S] to [4Fe-4S] cluster conversion in Escherichia coli biotin synthase. Biochemistry 36, 11811–11820 (1997).
Pasek, M. A., Kee, T. P., Bryant, D. E., Pavlov, A. A. & Lunine, J. I. Production of potentially prebiotic condensed phosphates by phosphorus redox chemistry. Angew. Chem. Int. Ed. 47, 7918–7920 (2008).
Burcar, B. et al. Darwin's warm little pond: a one-pot reaction for prebiotic phosphorylation and the mobilization of phosphate from minerals in a urea-based solvent. Angew. Chem. Int. Ed. 55, 13249–13253 (2016).
Venkateswara Rao, P. & Holm, R. H . Synthetic analogues of the active sites of iron–sulfur proteins. Chem. Rev. 104, 527–559 (2004).
Ranjan, S. & Sasselov, D. D. Influence of the UV environment on the synthesis of prebiotic molecules. Astrobiology 16, 68–88 (2016).
Braterman, P. S., Cairns-Smith, A. G., Sloper, R. W., Truscott, T. G. & Craw, M. Photo-oxidation of iron(II) in water between pH 7.5 and 4.0. J. Chem. Soc. Dalton Trans. 7, 1441–1445 (1984).
Lill, R. Function and biogenesis of iron–sulphur proteins. Nature 460, 831–838 (2009).
Qi, W. & Cowan, J. A. Structural, mechanistic and coordination chemistry of relevance to the biosynthesis of iron–sulfur and related iron cofactors. Coord. Chem. Rev. 255, 688–699 (2011).
Mihara, H. & Esaki, N. Bacterial cysteine desulfurases: their function and mechanisms. Appl. Microbiol. Biotechnol. 60, 12–23 (2003).
Liu, Y. et al. A [3Fe–4S] cluster is required for tRNA thiolation in archaea and eukaryotes. Proc. Natl Acad. Sci. USA 113, 12703–12708 (2016).
Gil, R., Silva, F. J., Pereto, J. & Moya, A. Determination of the core of a minimal bacterial gene set. Microbiol. Mol. Biol. Rev. 68, 518–537 (2004).
Rapf, R. J. & Vaida, V. Sunlight as an energetic driver in the synthesis of molecules necessary for life. Phys. Chem. Chem. Phys. 18, 20067–20084 (2016).
Kim, J. H., Bothe, J. R., Alderson, T. R. & Markley, J. L. Tangled web of interactions among proteins involved in iron–sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies. Biochim. Biophys. Acta 1853, 1416–1428 (2015).
Lide, D. R. (ed.) CRC Handbook of Chemistry and Physics 84th edn (CRC, 2003).
Yang, C. S. & Huennekens, F. M. Iron–mercaptoethanol–inorganic sulfide complex. Possible model for chromophore of nonheme iron proteins. Biochemistry 9, 2127–2133 (1970).
Sugiura, Y. & Tanaka, H. Iron–sulfide chelates of some sulfur-containing peptides as model complex of non-heme iron proteins. Biochem. Biophys. Res. Commun. 46, 335–340 (1972).
Mansy, S. S. & Szostak, J. W. Reconstructing the emergence of cellular life through the synthesis of model protocells. Cold Spring Harb. Symp. Quant. Biol. 74, 47–54 (2009).
Stano, P. & Luisi, P. L. Achievements and open questions in the self-reproduction of vesicles and synthetic minimal cells. Chem. Commun. 46, 3639–3653 (2010).
Monnard, P., Apel, C. L., Kanavarioti, A. & Deamer, D. W. Influence of ionic inorganic solutes on self-assembly and polymerization processes related to early forms of life: implications for a prebiotic aqueous medium. Astrobiology 2, 139–152 (2002).
Adamala, K. & Szostak, J. W. Nonenzymatic template-directed RNA synthesis inside model protocells. Science 342, 1098–1100 (2013).
Belmonte, L. & Mansy, S. S. Metal catalysts and the origin of life. Elements 12, 413–418 (2016).
Hsiao, C. et al. RNA with iron(II) as a cofactor catalyses electron transfer. Nat. Chem. 5, 525–528 (2013).
The authors acknowledge the Simons Foundation (290360 to D.D.S., 290363 to J.W.S., 290362 to J.D.S., 290358 to S.S.M.), the Armenise-Harvard Foundation (to S.S.M.), COST action CM1304 (to C.B., J.D.S. and S.S.M.) and the University of Hull (to D.J.E. and S.Sh.) for funding. The authors thank L. Belmonte, C. Caumes, E. Izgu, E. Godino, N. Kamat, A. Mariani, T. Olsen, D. Rossetto, Z. Todd, O.D. Toparlak, A. Trifonov and M. Tsanakopoulou for discussions.
The authors declare no competing financial interests.
About this article
Cite this article
Bonfio, C., Valer, L., Scintilla, S. et al. UV-light-driven prebiotic synthesis of iron–sulfur clusters. Nature Chem 9, 1229–1234 (2017). https://doi.org/10.1038/nchem.2817
Nature Communications (2021)
Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters
JBIC Journal of Biological Inorganic Chemistry (2019)
Nature Catalysis (2018)
Prebiotic iron–sulfur peptide catalysts generate a pH gradient across model membranes of late protocells
Nature Catalysis (2018)