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The biogenesis of iron-sulfur centers, a very ancient origin


Iron-sulfur (Fe-S) clusters are protein cofactors essential for life. It is believed that iron-sulfur clusters are synthesized via complex multiprotein cellular machineries that are thought to have arisen in response to increased oxygen on Earth. The results of a recent study by researchers at IRIG indicate that the specific machinery for Fe-S biosynthesis is in fact much older. Their origin dates back to the last universal common ancestor (LUCA), long before the oxygenation of the atmosphere.

Published on 23 February 2023

​Fe-S clusters are protein cofactors essential to life. They result from the assembly between ferrous and/or ferric ions and sulfide ions. Present in proteins, they are involved in many essential cellular processes. It has been proposed for a long time in the field of Fe-S assembly that in an oxygen-free atmosphere, rich in iron and sulfur, Fe-S were formed spontaneously. With the appearance of a high concentration of oxygen on Earth, 2.4 billion years ago, the mechanisms of Fe-S cluster formation changed, in particular because of the oxidation of bioavailable iron and the presence of reactive oxygen species. Thus, organisms adapted by developing specific protein systems for Fe-S cluster biosynthesis (NIF, ISC and SUF), allowing Fe-S clusters to be synthesized in a controlled manner.

However, a recent study proposes a different scenario. Teams of researchers at IRIG [collaboration with Institut Pasteur, Paris] have combined their expertise to study the evolutionary history of the biogenesis machinery of Fe-S clusters. Using a genomic approach, by analyzing more than 10,000 genomes, the researchers identified two new machineries named MIS and SMS, present in many prokaryotes and dating back to the last universal common ancestor (LUCA). The scientists have characterized at the molecular level by biochemical approaches one of these two machineries (SMS), showing that it is indeed a system involved in the assembly of Fe-S clusters. Very ancient, these MIS and SMS machineries have then evolved in bacteria to give rise to the three machineries NIF, ISC and SUF.

This work shows that the assembly machinery of Fe-S clusters did not appear with oxygenation on Earth but well before, and opens new perspectives for the understanding of the very first metabolisms related to the origin of life.


Figure: Scenario for the origin and evolution of the biogenesis machinery of iron-sulfur clusters with reconstruction of ancestral systems and main evolutionary events.

NIF: Nitrogen Fixation
ISC: Iron Sulfur Cluster
SUF: SUlFur
SMS: Suf-like Minimal System
MIS: Minimal Iron Sulfur

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