UV-light-driven prebiotic synthesis of iron-sulfur clusters
Open accessAbstract
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.
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The inherent catalytic activity of simple cysteinyl peptides makes them an excellent starting point from which to evolve more complex (folded) enzymes and catalysts for protometabolic reactions.
“The inherent catalytic activity of simple cysteinyl peptides makes them an excellent starting point from which to evolve more complex (folded) enzymes (14, 39) and catalysts for protometabolic reactions in an abiotic environment.”
From Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water (2020) · cites this paper as [14]
The Abstract proposes that short peptides could assemble and stabilize catalytically active iron–sulfur clusters, and describes increased redox-catalyst activity when a tripeptide is extended to a dodecapeptide. The Discussion suggests these peptide–cluster complexes could have affected protometabolic processes, but says their functional impact remains unknown. It does not establish inherent catalytic activity of the peptides themselves or their evolution into folded enzymes. (LLM, conf=0.84)
Experimental — accuracy not yet measuredConceiving of a suitable venue with high temperatures or exposure to ultraviolet radiation or lightning which also leads to the accumulation of organic molecules in high concentrations is very challenging.
“Thus, conceiving of a suitable venue with high temperatures or exposure to ultraviolet radiation or lightning which also leads to the accumulation of organic molecules in high concentrations is very challenging [29,78,79].”
From Opinion: The Key Steps in the Origin of Life to the Formation of the Eukaryotic Cell (2024) · cites this paper as [78]
The Results describe UV-driven synthesis and report ligand concentrations used in experiments, while the Discussion describes light-exposed environments as compatible with iron-sulfur cluster formation. Neither section addresses whether finding a venue that combines high temperatures, UV radiation, or lightning with the accumulation of concentrated organic molecules is challenging. Searches for that combination and for organic-molecule accumulation found no supporting passage; page numbers were not available in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredIn almost all scenarios for the origin of life, both terrestrial and marine, the initial catalysts are assumed to have involved transition metals particularly Fe and Ni with sulphur.
“In almost all scenarios for the origin of life, both terrestrial and marine, the initial catalysts are assumed to have involved transition metals particularly Fe and Ni with sulphur (Table 2, property 9) [16,51,135,137,151,152,153], although more recently a wider net has been cast [154,155].”
From ‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life (2021) · cites this paper as [153]
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“Ultraviolet light has been championed by John Sutherland (1962–) and others [30,37], given that it can be used to energize the synthesis of a number of important precursor biochemicals including purines and pyrimidines [29,31,32,78].”
Background
- Authors
- 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.
- Affiliations
- University of Trento (IT)
- University of Hull (GB)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Mansy, Sheref S.
- ORCID
- Venue
- Nature Chemistry
- Published
- 2017-07-10
- Volume
- 9
- Issue
- 12
- Pages
- 1229-1234
- ISSN
- 1755-4330 (ISSN-L)
- 1755-4349
- PMC
- PMC5808832
- OpenAlex
- W2735781658
- Cited by
- 158
- References
- 36
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 22 · 2023: 19 · 2022: 20 · 2021: 20 · 2020: 20 · 2019: 11 · 2018: 13 · 2017: 6
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Repository@Hull (Worktribe) (University of Hull) (acceptedVersion, cc-by)
- Repository@Hull (Worktribe) (University of Hull) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Iris (University of Trento) (submittedVersion, other-oa)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Giovanni Armenise-Harvard Foundation
- University of Hull
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Paleontology and Stratigraphy of Fossils
- Keywords
- iron-sulfur clusters, prebiotic synthesis, ultraviolet radiation, photooxidation, ferrous ions, photolysis, cysteine-containing peptides, origin of life, early Earth, cofactors
- MeSH terms
- Origin of Life, Iron-Sulfur Proteins, Ultraviolet Rays, Evolution, Chemical
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