Fe-S cluster biogenesis by the bacterial Suf pathway.

Biogenesis of iron-sulfur (Fe-S) clusters in an essential process in living organisms due to the critical role of Fe-S cluster proteins in myriad cell functions. During biogenesis of Fe-S clusters, multi-protein complexes are used to drive the mobilization and protection of reactive sulfur and iron intermediates, regulate assembly of various Fe-S clusters on an ATPase-dependent, multi-protein scaffold, and target nascent clusters to their downstream protein targets. The evolutionarily ancient sulfur formation (Suf) pathway for Fe-S cluster assembly is found in bacteria and archaea. In Escherichia coli, the Suf pathway functions as an emergency pathway under conditions of iron limitation or oxidative stress. In other pathogenic bacteria, such as Mycobacterium tuberculosis and Enterococcus faecalis, the Suf pathway is the sole source for Fe-S clusters and therefore is a potential target for the development of novel antibacterial compounds. Here we summarize the considerable progress that has been made in characterizing the first step of mobilization and protection of reactive sulfur carried out by the SufS-SufE or SufS-SufU complex, Fe-S cluster assembly on SufBC2D scaffold complexes, and the downstream trafficking of nascent Fe-S clusters to A-type carrier (ATC) proteins.

铁 - 硫（Fe - S）簇的生物合成在生物体内是一个重要过程，因为Fe - S簇蛋白在众多细胞功能中起着关键作用。在Fe - S簇生物合成过程中，多蛋白复合物用于驱动活性硫和铁中间体的动员和保护，在依赖ATP酶的多蛋白支架上调节各种Fe - S簇的组装，并将新生的簇靶向其下游蛋白质靶点。在细菌和古菌中发现了用于Fe - S簇组装的在进化上古老的硫形成（Suf）途径。在大肠杆菌中，Suf途径在铁限制或氧化应激条件下作为一种应急途径发挥作用。在其他病原菌中，如结核分枝杆菌和粪肠球菌，Suf途径是Fe - S簇的唯一来源，因此是开发新型抗菌化合物的一个潜在靶点。在此，我们总结了在表征由SufS - SufE或SufS - SufU复合物进行的活性硫的动员和保护的第一步、SufBC₂D支架复合物上的Fe - S簇组装以及新生Fe - S簇向下游的A型载体（ATC）蛋白的转运方面所取得的重大进展。