Life without Fe–S clusters

Summary Fe– S clusters are critically important cofactors implicated in numerous cellular processes, including respiration, amino acid biosynthesis, cofactor biosynthesis, t RNA modification, DNA repair and regulation of gene expression. In the accompanying manuscript, Tanaka et al . show that reengineering of the isoprenoid biosynthetic pathway in E . coli (to bypass the usage of essential F e– S cluster proteins by inserting the mevalonate pathway) can offset the indispensability of the F e– S cluster biosynthetic systems. They show that the resulting Δisc Δsuf double mutants supplemented with mevalonate can grow slowly without detectable F e– S cluster proteins. This result is astounding and raises interesting questions about what is essential and what is dispensable in the compendium of F e– S cluster protein functions in this cell.