Interplay between Oxygen and Fe–S Cluster Biogenesis: Insights from the Suf Pathway

Iron–sulfur (Fe–S)
cluster metalloproteins conduct
essential functions in nearly all contemporary forms of life. The
nearly ubiquitous presence of Fe–S clusters and the fundamental
requirement for Fe–S clusters in both aerobic and anaerobic
Archaea, Bacteria, and Eukarya suggest that these clusters were likely
integrated into central metabolic pathways early in the evolution
of life prior to the widespread oxidation of Earth’s atmosphere.
Intriguingly, Fe–S cluster-dependent metabolism is sensitive
to disruption by oxygen because of the decreased bioavailability of
ferric iron as well as direct oxidation of sulfur trafficking intermediates
and Fe–S clusters by reactive oxygen species. This fact, coupled
with the ubiquity of Fe–S clusters in aerobic organisms, suggests
that organisms evolved with mechanisms that facilitate the biogenesis
and use of these essential cofactors in the presence of oxygen, which
gradually began to accumulate around 2.5 billion years ago as oxygenic
photosynthesis proliferated and reduced minerals that buffered against
oxidation were depleted. This review highlights the most ancient of
the Fe–S cluster biogenesis pathways, the Suf system, which
likely was present in early anaerobic forms of life. Herein, we use
the evolution of the Suf pathway to assess the relationships between
the biochemical functions and physiological roles of Suf proteins,
with an emphasis on the selective pressure of oxygen toxicity. Our
analysis suggests that diversification into oxygen-containing environments
disrupted iron and sulfur metabolism and was a main driving force
in the acquisition of accessory Suf proteins (such as SufD, SufE,
and SufS) by the core SufB–SufC scaffold complex. This analysis
provides a new framework for the study of Fe–S cluster biogenesis
pathways and Fe–S cluster-containing metalloenzymes and their
complicated patterns of divergence in response to oxygen.