Nitrogen is essential for life. It's needed to build proteins, DNA and many other components of cells. Although nitrogen gas makes up almost 80 percent of the earth's atmosphere, most organisms cannot use it directly. Certain microbes solve this problem through a process called nitrogen fixation, which converts nitrogen gas into ammonia. This process is carried out by an enzyme called nitrogenase.
Understanding how this enzyme functions could have huge implications for the more efficient and biologically-based production of ammonia, a crucial component of common fertilizers.
A collaborative research team from across the U.S., initiated by a research group at the University of Arkansas, studied nitrogenase and its regulation in a methane-producing microbe known as a methanogen. Using high-resolution cryo-electron microscopy, they discovered that methanogen nitrogenase can bind with regulatory proteins to form a large inactive complex - what the authors call a protein supercomplex.
The newly identified supercomplex functions as a molecular off switch, preventing nitrogen fixation when energy or nutrients are limited. Signals that reflect the cell's energy and nutrient levels can break apart this complex and restore enzyme activity, allowing nitrogen fixation to resume.
"This discovery reveals an entirely new strategy for regulating one of the most important biochemical reactions on Earth," said Dan Lessner, professor of biological sciences at the University of Arkansas and corresponding author of the study.
The finding was published in Nature , and is important because nitrogen fixation supports agriculture, food production and ecosystems around the world. It also advances understanding of microbial physiology, the global nitrogen cycle and the evolution of nitrogen fixation while providing insights that could inform future biotechnology and sustainable agriculture applications.
"The biggest limitation in the growth of plants is often having access to enough nitrogen, even when they have enough sunlight, water and CO2 ," explained Lessner. "If they don't have enough nitrogen, you're not going to grow very big plants, especially in terms of providing plant material for humans and animals."
He adds that current fertilizer production chemically converts nitrogen from the atmosphere into ammonia in high-pressure reactors powered by fossil fuels. The resulting nitrogen-based fertilizer is then spread on fields in hopes that the plants will absorb it. During this process, a significant amount of that fertilizer runs off the land into streams and waterways, which can lead to algal blooms from eutrophication, habitat degradation and biodiversity loss.
"This enzyme [nitrogenase] can do the conversion biologically under standard temperature and pressure," Lessner continued. "There's a lot of interest in understanding how this enzyme works and how it catalyzes this reaction. That's because we can potentially use it as a catalyst in a more energy efficient and environmentally friendly way to produce ammonia for fertilizer. Because our studies are genetically based, we could potentially take the genetic information we've learned and move it into plants, such as corn.
"This would allow plants to potentially fix their own nitrogen from the atmosphere and alleviate the need for fertilizer, which would obviously have huge economic, social and environmental impacts," he said.
Lessner's co-authors on the study included Rajnandani Kashyap, Thomas M. Deere, Ahmed Dhamad, Melissa Chanderban, Monika Tokmina-Lukaszewska, Brian Bothner and Edwin Antony. Deere, Dhamad and Chanderban are or were affiliated with the U of A at the time the work was done.
Nature
Computational simulation/modeling
Cells
Cryo-EM structure of a methanogen nitrogenase–PII protein supercomplex
7-Oct-2026
The authors declare no competing interests.