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January 15, 2025

Protein that protects biological nitrogen fixation from oxidative stress could reduce reliance on synthetic fertilizers

Structure of the O2-protected FeSII–nitrogenase complex. Credit: Nature (2025). DOI: 10.1038/s41586-024-08355-3
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Structure of the O2-protected FeSII–nitrogenase complex. Credit: Nature (2025). DOI: 10.1038/s41586-024-08355-3

An oxygen sensor protein protects the enzymatic machinery of biological nitrogen fixation from serious damage, and its use in biotechnology could help to reduce the use of synthetic fertilizer in agriculture in the future.

A research team led by biochemist Prof. Dr. Oliver Einsle from the Faculty of Chemistry and Pharmacy and the Center for Biological Signaling Studies (BIOSS) at the University of Freiburg, using the newly established cryo-electron microscopy in Freiburg, has discovered exactly how the so-called Shethna protein II works . Their study has been in the journal Nature.

Nitrogen fertilizer is ecologically problematic

The element nitrogen is an essential component of all living organisms; in agriculture, it is often added as fertilizer to enable high yields over the long term. However, the production and application of these fertilizers is problematic in terms of energy and the environment.

For years, attempts have therefore been made to transfer the natural nitrogen fixation in bacteria and archaea to crops. The enzyme is responsible for the binding of nitrogen. One of the most serious problems with the transfer to plants is that nitrogenase is extremely sensitive to , which is produced by plants themselves during the process of photosynthesis.

Sequential formation of the protected FeSII:NifH:NifDK complex. Credit: Nature (2025). DOI: 10.1038/s41586-024-08355-3
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Sequential formation of the protected FeSII:NifH:NifDK complex. Credit: Nature (2025). DOI: 10.1038/s41586-024-08355-3

Shethna protein II forms a complex with the enzyme nitrogenase

Philipp Franke, Simon Freiberger and Dr. Lin Zhang from the team led by Prof. Oliver Einsle has now been able to show how a small factor, the Shethna protein II, registers an increase in . It then very quickly forms a complex with the two components of the enzyme nitrogenase, which protects them from .

In this process, the activated Shethna protein II binds the much larger nitrogenase and its associated reductase, forming long filaments with both proteins in which oxygen cannot reach the active centers of the nitrogenase. As soon as the cells overcome this , the complex dissolves and the can resume its work.

Use in plant cells is conceivable

Even if nitrogenase is produced directly in plant cells, it is likely that such short stress phases with increased oxygen concentrations will occur again and again. In the case of biotechnological use, the co-production of the small Shethna protein II could then help to protect the elaborately synthesized enzymes in their new environment and maintain their function in the plant cell.

"The production of functioning nitrogenase in plants would initiate a in green biotechnology, and this small protein can make a decisive contribution to making this possible," says Einsle.

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More information: Philipp Franke et al, Conformational protection of molybdenum nitrogenase by Shethna protein II, Nature (2025).

Journal information: Nature

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An oxygen sensor protein, Shethna protein II, protects nitrogenase from oxidative damage by forming a complex that shields it from oxygen. This mechanism could enable the transfer of biological nitrogen fixation to crops, potentially reducing reliance on synthetic fertilizers. The co-production of Shethna protein II in plant cells could maintain nitrogenase function despite oxidative stress, marking a significant advancement in green biotechnology.

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