Nitrogen fixation breakthrough: Nature study finds “off switch” that locks 3 nitrogenase units

A U.S. research team has discovered a molecular “off switch” that controls nitrogen fixation in an ancient methane-producing microbe, a finding the authors say could eventually help engineer crops that supply part of their own nitrogen. The study, published October 7 in Nature, describes for the first time the structure of a native nitrogenase from a methanogen, and it looks nothing like the bacterial version scientists have relied on for decades.

The work matters for the fertilizer industry because nitrogenase is the only enzyme in nature that turns atmospheric nitrogen into ammonia at ordinary temperature and pressure. Industrial ammonia, by contrast, depends on the Haber-Bosch process, which runs at high pressure on fossil-fuel energy. Every new insight into how nitrogenase is switched on and off widens the toolkit for biological nitrogen products and, in the longer term, for nitrogen-fixing cereals.

How the nitrogen fixation off switch works

The team, led by Daniel Lessner at the University of Arkansas and Edwin Antony at Saint Louis University School of Medicine, studied nitrogenase in Methanosarcina acetivorans, a methanogen. Using cryo-electron microscopy (cryo-EM), they found that the enzyme’s catalytic NifDK units can assemble with regulatory PII proteins into a large, inactive supercomplex.

In that structure, three NifDK units are bridged by six copies of a heterotrimeric PII complex known as NifI_1,2. The bridging proteins block the enzyme’s partner protein from docking, which locks nitrogenase in an inactive state. According to the University of Arkansas, signals that reflect the cell’s energy and nutrient status can break the complex apart and restore activity, so nitrogen fixation resumes only when the cell can afford it.

“This discovery reveals an entirely new strategy for regulating one of the most important biochemical reactions on Earth,” said Lessner, professor of biological sciences at the University of Arkansas and corresponding author.

Why nitrogenase regulation matters for fertilizer

Nitrogen fixation is energy-hungry for microbes, and cells shut it down tightly when resources are scarce. That regulation is one of the main obstacles for companies trying to keep engineered microbes fixing nitrogen in a farmer’s field, where conditions change hour by hour.

Lessner tied the work directly to fertilizer. He noted that plant growth is often limited by nitrogen even when light, water and carbon dioxide are sufficient, and that fertilizer applied to fields partly runs off into waterways.

“This enzyme can do the conversion biologically under standard temperature and pressure,” he said, adding that because the research is genetically based, the team “could potentially take the genetic information we’ve learned and move it into plants, such as corn.”

Antony framed the result as a correction to textbook models. “For decades, scientists have relied on a model of nitrogenase based on what we observed in common bacteria,” he said. “This discovery demonstrates that nature has evolved alternative ways to accomplish the same chemistry, giving us an entirely new framework for understanding biological nitrogen fixation.”

What is cryo-EM?

Cryo-electron microscopy freezes proteins in thin ice and images thousands of copies from different angles, then combines them into a 3D model. Nitrogenase is destroyed by oxygen, so the Saint Louis University team built workflows that kept samples strictly oxygen-free during preparation and imaging. The University of Arkansas group spent several years engineering the microbe and isolating the native protein before the imaging began.

From lab structure to field products

The study is fundamental research. It does not report a crop trial, and no commercial product is attached to it. Its value for the nitrogen market is in mechanism: knowing exactly how a natural off switch is built gives engineers a target to disable or tune when designing microbes or plants that fix nitrogen more reliably.

That is the same problem biological nitrogen suppliers are working on commercially. Fertilizer Daily has tracked several approaches, from hydrogel beads that deliver nitrogen-fixing bacteria to cereal roots to light-driven nanocrystal–nitrogenase systems that convert atmospheric nitrogen into ammonia.

The research was funded by the U.S. Department of Energy and involved the University of Arkansas, Saint Louis University and Montana State University. The authors declared no competing interests.

The next question is whether similar regulatory switches can be found, or deliberately removed, in the bacteria that colonize crop roots. If they can, the long-standing goal of cutting synthetic nitrogen through biology moves from structural biology toward agronomy.

Source: Phys.org