The oxygen effector pathway, regulated by the Fnr (fumarate and nitrate reduction) regulog, plays a key role in enabling facultative anaerobic bacteria to adapt to changes in oxygen availability. Fnr is a global transcriptional regulator that senses oxygen levels through an iron-sulfur cluster. Under anaerobic (low oxygen) conditions, Fnr is activated and modulates gene expression to favor anaerobic respiration or fermentation, while repressing aerobic metabolic pathways. In this context, Fnr also regulates genes involved in central carbon metabolism, including the glyoxylate shunt, which provides an alternative to the TCA cycle under specific growth conditions such as limited oxygen or carbon. It facilitates the adaptation to anaerobic growth conditions by regulating the expression of gene products that are involved in anaerobic energy metabolism. When the terminal electron acceptor, O2, is no longer available, it represses the synthesis of enzymes involved in aerobic respiration and increases the synthesis of enzymes required for anaerobic respiration. FNR senses the oxygen concentration directly via the disassembly and reassembly of the [4Fe-4S] clusters. Anaerobic, de novo acquisition of the iron-sulfur cluster converts monomeric, inactive apo-FNR into a dimeric form containing two [4Fe-4S] clusters. This, in turn, enhances the affinity of FNR for specific DNA targets and mediates transcription regulation by establishing direct FNR-RNA polymerase contacts. Key genes in the Fnr regulog include: aceA – Encodes isocitrate lyase, an enzyme that bypasses the decarboxylation steps of the TCA cycle, allowing the cell to conserve carbon by converting isocitrate into succinate and glyoxylate. aceB – Encodes malate synthase, which condenses glyoxylate and acetyl-CoA to form malate, completing the glyoxylate shunt.

Oxygen - Fnr References