sufABCDSE

The sufABCDSE operon encodes six proteins—SufA, SufB, SufC, SufD, SufS, and SufE—that participate in the biosynthesis and delivery of iron–sulfur (Fe–S) clusters in many bacteria. Known as the SUF system, it provides an alternative to the housekeeping ISC pathway and is particularly important under conditions that promote Fe–S cluster damage, such as oxidative or nitrosative stress and/or iron limitation.

SufS is a cysteine desulfurase that mobilizes sulfur from cysteine; SufE acts as a small sulfur transfer protein that accepts persulfide sulfur from SufS. SufA functions as an Fe–S cluster carrier that can deliver clusters to apoenzymes. SufB, SufC, and SufD form a protein complex that acts as an Fe–S assembly scaffold and, in the case of SufC, provides energy through ATP hydrolysis to drive cluster assembly and trafficking.

During Fe–S cluster biogenesis via the SUF system, sulfur is transferred from SufS to SufE, which then feeds sulfur to the SufB–SufC–SufD assembly scaffold. Iron is delivered to the scaffold and assembled clusters are handed off to SufA for delivery to apoenzymes. Although the exact order and molecular details are still studied, the SUF machinery can assemble functional Fe–S clusters even when the ISC system is compromised or when cells experience oxidative stress.

Expression of sufABCDSE is induced under stress conditions and iron limitation, and its regulation integrates with cellular redox and iron homeostasis networks. In many bacteria, transcriptional control involves redox-responsive regulators and is coordinated with the ISC system to balance Fe–S cluster biogenesis.

Distribution and significance: the SUF operon is widespread in bacteria and some archaea, often present as sufABCDSE in a single operon. It is essential for survival under damaging conditions and contributes to the assembly of Fe–S–dependent enzymes involved in respiration, metabolism, and DNA replication. It is a focus of study for understanding bacterial stress responses and for potential antimicrobial targets.