Microorganisms capable of producing nitrogen for plants on their own could become an alternative to conventional fertilizers, whose production depends on fossil fuels. However, despite decades of research, developers have yet to achieve consistent performance from such solutions in agriculture. An international team of scientists has proposed four priority areas that should bring biological nitrogen fertilizers closer to commercial use. The work was published in the journal Nature Biotechnology.

The commentary, titled “The Next Frontier in Nitrogen Fixation,” was led by the American biotechnology company Switch Bioworks. Its specialists contributed to the article alongside researchers from the University of Oxford, the University of Wisconsin–Madison, the Federal University of Paraná in Brazil, and the John Innes Centre.

Why Bacteria Are Not Yet a Fully Viable Alternative to Fertilizers

Nitrogen fertilizers are essential to modern agriculture. Cereal crops, including corn, wheat, and rice, provide about half of the calories consumed by humanity and depend on a supply of nitrogen to maintain high yields. Meanwhile, conventional fertilizer production relies heavily on fossil fuels, and fertilizer use contributes to greenhouse gas emissions and water pollution.

Some bacteria can fix atmospheric nitrogen, converting it into compounds that plants can use. However, naturally occurring microorganisms have a particular trait: they retain most of the nitrogen they produce for their own growth.

Genetic engineering can alter their behavior and make them release ammonia that is available to plants. But this creates another problem: nitrogen production can weaken the bacteria’s ability to reproduce, establish themselves on roots, and compete with other microorganisms.

Further challenges arise because bacteria do not always colonize roots equally well in different soil types. They may also lack sufficient energy from plant root exudates. All of this makes it difficult to ensure consistent performance from biological fertilizers under real-world field conditions.

Four Priorities for Advancing the Technology

The authors identified four areas that should help overcome the existing limitations.

The first is to create diverse microbial communities capable of establishing themselves on roots and working effectively under a range of soil conditions. Using multiple species of microorganisms could make the technology more resilient to differences between fields.

The second is to develop genetic systems that separate bacterial growth from nitrogen production. The proposed approach involves allowing microorganisms to multiply and establish themselves on roots first, and then activate nitrogen production. This would prevent nitrogen production from interfering with the bacteria’s successful development.

The third area involves modifying the characteristics of the plants themselves so that they better support nitrogen-fixing microorganisms and provide them with the resources they need.

The fourth is to develop rigorous standards for evaluating effectiveness. The scientists emphasize that increased plant growth alone does not prove that bacteria have actually transferred fixed nitrogen to the plants. Confirming this requires dedicated studies, followed by field trials that monitor root colonization and nitrogen content in plants.

From Laboratory Research to the Field

Separating microbial growth from nitrogen production already underpins Switch Bioworks’ technology. The company uses genetic switches that allow bacteria to first establish themselves and multiply on roots before shifting to nitrogen production. In parallel, it is developing machine learning methods to create diverse microbial communities intended to remain effective under varying field conditions.

The company has also announced a strategic collaboration with Bayer Crop Science focused on advancing approaches to developing biological nitrogen fertilizers.

According to the commentary’s authors, even a partial replacement of conventional fertilizers could deliver substantial environmental benefits. If biological solutions can replace 10–20% of conventional nitrogen fertilizers, annual emissions could be reduced by tens of millions of metric tons of CO₂ equivalent. Nitrogen losses from agricultural fields would also decrease, and farmers could lower their costs.

However, bringing these technologies to market will require further genetic engineering, large-scale field trials, and regulatory review. Switch Bioworks reports that it has already received first-in-class authorizations from the U.S. Department of Agriculture and the U.S. Environmental Protection Agency, as well as approval from Brazil’s National Technical Commission on Biosafety.