NifL

NifL is a redox-sensitive regulatory flavoprotein found in several nitrogen-fixing bacteria, where it functions as an anti-activator of NifA, the transcriptional activator of nif genes. The NifL–NifA system forms a central regulatory switch that couples environmental cues to the expression of nitrogenase genes, allowing bacteria to balance energy-intensive nitrogen fixation with nutrient availability.

In many diazotrophs, NifL binds to NifA under conditions of high oxygen tension or when fixed nitrogen (such as ammonia) is abundant, inhibiting NifA’s activation of nif operons and preventing nitrogenase production. When oxygen is scarce and fixed nitrogen is limited, NifL undergoes a redox-driven conformational change that reduces its affinity for NifA, allowing NifA to activate transcription of nif genes through sigma-54 and thus promote nitrogen fixation.

NifL contains sensor and regulatory regions that detect the cell’s redox state, often via interactions with flavin cofactors and electron transfer partners. The signaling state of NifL integrates signals related to oxygen availability and nitrogen status to control the activity of NifA.

Biological significance and distribution: The NifL–NifA regulatory pair is central to controlling nitrogen fixation in bacteria possessing the nif gene cluster. While the precise regulatory architecture can vary among species, the general mechanism involves NifL acting as an anti-activator of NifA in response to O2 and fixed nitrogen, with relief of inhibition under low-oxygen, nitrogen-starved conditions to enable nif gene expression.

History and nomenclature: NifL and NifA were identified as components of the nif regulatory system in nitrogen-fixing bacteria in the late 20th century and have since been studied to understand how diazotrophs regulate nitrogenase gene expression.