Can microbes replace synthetic fertilizer?

On his farm in Dawson County, Nebraska, Don Batie is always looking for ways to grow more corn with fewer chemicals. He’s concerned about the health and environmental impacts of excess nitrogen fertilizer leaching into the area’s groundwater, so he has been investigating ways to reduce the amount he uses.

In 2021, he started testing a new product from Pivot Bio: genetically modified microbes that pull N₂ out of the air and convert it into a form of nitrogen that plants can use. The company says the approach allows farmers to cut their use of synthetic fertilizer, reducing water pollution and greenhouse gas emissions.

That first year, Batie was hopeful, but he applied too much synthetic fertilizer to tell if the microbes were working. The following year, he set up an experiment to test the microbes on areas with less fertilizer. A major drought made it hard to draw conclusions.

“I have a feeling it tends to work. I’m sticking with it,” he says. “If it doesn’t show up this year, will I try it again? Maybe not. I’ll go with something different. But I’m willing to give it a fair trial.”

Concern about groundwater isn’t the only reason farmers are looking for fertilizer alternatives. Fertilizer prices climbed to dizzying heights in 2021 and remained elevated through 2022, pushing many farmers to look for other options. Microbial fertilizers offer a solution, and over the past several years they have gained momentum.

Farmers used Pivot Bio’s product on more than 1.2 million hectares (ha) in the US last year, up from 400,000 ha in 2021. Azotic Technologies, another firm, started selling US farmers a nitrogen-producing microbe in 2019 and registered the product in the European Union in 2022. Start-ups like Kula Bio and Switch Bioworks also want to introduce microbial fertilizers.

Agricultural giants are getting in on the action too. Bayer is working with Ginkgo Bioworks to genetically engineer a nitrogen-producing microbe. Earlier this year, Corteva Agriscience closed on its acquisition of the biofertilizer company Symborg.

Although companies are betting on microbes, some farmers and agricultural scientists are skeptical that they work as advertised. In April, a group of agricultural extension researchers published a collection of studies suggesting that microbial fertilizer products don’t provide much benefit.

Biofertilizer companies are pushing back, arguing that their own studies show that the products are effective. They say their microbes could be powerful tools to rein in the negative effects of synthetic fertilizer without reducing food production. But first, they have to persuade farmers to use the microbes.

Batie is almost convinced. Over the years, he’s tested dozens of new agricultural technologies on his farm. Many of the products failed, so he tends to be skeptical. But his instincts tell him that Pivot Bio could be a winner.

“I really want this to work. I’m hoping it will,” he says. “Walking through the plots, I felt like it was working.”

Nature’s fertilizer

Nitrogen, phosphorus, and potassium are three of the most important nutrients plants need and the main components of chemical fertilizers. While natural forms of phosphorus and potassium come from the earth, released into the soil through the weathering of rocks or the decomposition of plants and animals, nitrogen mostly comes from the air.

More than three-quarters of Earth’s atmosphere is composed of N₂, an inert form of nitrogen that plants can’t use. But the soil is teeming with naturally occurring microbes that employ an enzyme to turn N₂ into reactive, plant-usable forms of nitrogen, a process called biological nitrogen fixation.

Many legumes, such as soybeans, have evolved nodules on their roots that house nitrogen-fixing bacteria and supply the bugs with sugar and nutrients. In return, the bacteria share nitrogen with their hosts, reducing the amount of fertilizer that legumes need.

In contrast, cereals like corn, rice, and wheat—which make up about half the calories people consume, according to the United Nations’ Food and Agriculture Organization—have not developed this symbiotic relationship with soil bacteria. Cereals can benefit from nitrogen-fixing microbes that live freely in the soil, but these bacteria alone don’t provide enough nitrogen for bountiful harvests.

For the past century, cereal farmers have relied on synthetic nitrogen fertilizers, which are made by combining nitrogen and hydrogen under intense pressure to form ammonia. Ammonia can be used as is or converted into other fertilizers, such as urea and ammonium phosphates.

The industrialization of synthetic fertilizer production during the early 20th century dramatically increased crop yields and arguably staved off starvation for much of the world’s growing population.

But flooding fields with fertilizer came with consequences, according to Benjamin Houlton, an environmental scientist at Cornell University. “As far as we can tell, life on this planet has never seen this amount of nitrogen,” he says. “That’s a Pandora’s box, from a global perspective.”

Nitrogen fertilizers account for about 5% of global greenhouse gas emissions, according to a recent estimate in Nature Food (2023, DOI: 10.1038/s43016-023-00698-w). Roughly a third of those emissions come from the processes used to make the fertilizers, which consume huge amounts of energy and can emit the powerful greenhouse gas nitrous oxide. The rest come after fertilizers are applied to a field, where microbes enzymatically convert fertilizers into more nitrous oxide.

In addition, about half the nitrogen applied to agricultural fields, on average, runs off into the environment, where it can degrade wildlife habitats and contaminate drinking water, according to a study in Environmental Research Letters (2014, DOI: 10.1088/1748-9326/9/10/105011).

The demand for nitrogen is only increasing as the world’s population grows, says James Galloway, a biogeochemist at the University of Virginia who studies the nitrogen cycle. He says it’s imperative to find ways to use nitrogen more efficiently to avoid hitting “an untenable environmental limit.”

Technology’s solution

As the damaging effects of synthetic nitrogen continue to pile up, companies like Azotic, Corteva, and Pivot Bio say the solution is microbes that can provide nitrogen to cereal crops.

Technologically, that’s a big challenge. Splitting N₂’s triple bond takes a lot of energy—regardless of whether the process takes place in a chemical factory or in bacteria—and microbes are loath to give up the hard-won fruits of their labor. In addition, microbes tend to slow their production of nitrogen when there’s already a lot of it in the soil.

Pivot Bio aims to overcome those hurdles through gene editing. The company was founded in 2011 by Alvin Tamsir and Karsten Temme while they were studying biological nitrogen fixation in Christopher Voigt’s lab at the University of California, San Francisco.

In 2019, Pivot Bio became one of the first companies to start marketing a nitrogen-fixing microbe for corn, selling out its initial production within 6 weeks. Since then, Pivot Bio has raised more than $500 million from investors and introduced nitrogen-fixing microbes for sorghum and spring wheat. Last year, the company reported more than $60 million in revenue.

Pivot Bio has edited the genes of Klebsiella variicola and Kosakonia sacchari, naturally occurring bacteria, so that they produce nitrogen even in the presence of synthetic fertilizer and more readily share it with plants, says Clayton Nevins, an agronomic scientist with the company. “If we’re fixing nitrogen, that’s great,” he says. “But we don’t want the microbe to just have all of it itself.”

The company’s goal is to eventually replace all synthetic nitrogen with microbes, says Temme, who serves as CEO. That’s a big jump from the 45 kg of nitrogen per ha the company says it can replace now, roughly a quarter of the nitrogen the average US corn farmer uses, according to US Department of Agriculture data. “We are still in the early innings,” Temme says. “From a technical perspective, we have a lot of room still to go.”

Forcing microbes to make nitrogen when they normally wouldn’t comes with a trade-off, according to Tim Schnabel, founder and CEO of Switch Bioworks, a start-up that is developing its own nitrogen-producing microbe. Using energy to make nitrogen for crops leaves microbes with less energy to spend on growth or other metabolic processes.

The year-old Switch, which doesn’t yet have a commercial product, hopes to solve this problem by designing a microbe that first focuses on colonizing the soil and only later switches to a state that produces and releases nitrogen. “We’re not trying to do both at the same time,” Schnabel says.

Kula Bio, another precommercial start-up, is pursuing a different approach to the energy issue. Instead of genetically modifying microbes, the company is equipping natural Xanthobacter autotrophicus bacteria with a fuel tank so they have enough energy to make plenty of nitrogen. The company grows its microbes in a bioreactor and then cuts off their nutrition supply. This puts the microbes under stress, so they start hoarding food and energy.

“It kind of fattens them up. Think about a bear prior to hibernation,” cofounder and CEO Bill Brady says. When the fattened microbes get into the soil, they simply draw on that store of energy to produce more nitrogen.

Tom Tregunno, director of commercialization for Azotic North America, claims that the nitrogen made by other companies’ microbes is vulnerable because it has to migrate to the plant through the soil. In contrast, Azotic’s nitrogen-fixing microbe, a bacterium called Gluconacetobacter diazotrophicus that was discovered in sugarcane, lives inside the plant. The product is applied where seeds are planted or sprayed onto leaves. It then migrates into a plant’s cells.

“You have this direct line,” Tregunno says. “The closer that bacteria is to the cell, the bigger the influence is going to be.”

Corteva’s product, a strain of Methylobacterium symbioticum that hasn’t been genetically modified, also lives in plant cells. The strain was originally developed by Symborg. Corteva started distributing the product for Symborg in April 2022 and announced plans to acquire the start-up later that year.

All these firms argue that microbes are a more efficient source of nitrogen than synthetic fertilizers. Many farmers add lots of fertilizer to their soil at the beginning of the season, which puts it at risk of washing away and causing pollution. But microbes trickle out nitrogen throughout the season, Temme says, making it more likely to go into a plant than a river. A recent Pivot Bio–funded study at Iowa State University found that experimental plots treated with synthetic fertilizer and the company’s microbes leached less nitrates than plots treated with synthetic fertilizer alone.

Deepesh Bista, an agricultural technology analyst with Lux Research, says there’s a lot to learn about the basic science behind these technologies, but he’s optimistic they’ll reduce farming’s dependence on synthetic fertilizer. He’s less convinced that farmers will be able to replace synthetic fertilizer completely, as some firms, such as Pivot Bio, say is possible.

“The technology is solid,” Bista says. “As we understand these things better, I’m bullish that these things will work down the road, but not alone.”

The doubters

Like other agricultural technologies that came before, nitrogen-fixing microbes have their doubters.

Earlier this year, a team of agricultural extension agents from 10 US universities published a collection of studies questioning the performance of nitrogen-fixing microbe products from Azotic, Corteva, Pivot Bio, and TerraMax.

Azotic and Pivot Bio claim that farmers can reduce their application of synthetic nitrogen and replace it with a nitrogen-​fixing microbe to maintain yields. And many of the trials found that farmers could indeed cut back on their typical rates of synthetic fertilizer without sacrificing yield.

But in most of those cases, yield was maintained regardless of whether a nitrogen-fixing microbe was used, says Daniel Kaiser, an extension researcher from the University of Minnesota Twin Cities who tested several nitrogen-fixing products for the collection of studies.

Kaiser says this is probably because most farmers apply too much fertilizer and can reduce their use without paying for a substitute product.

“A lot of the so-called wins that these companies are claiming are situations where farmers are . . . already overapplying,” he says. “They’re going to get the same yield whether they apply the [microbe] or not.”

Dan Poston, Pivot Bio’s vice president of field R&D, argues that focusing on yield doesn’t provide a complete picture of a nitrogen-fixing microbe’s performance. He agrees that most farmers apply more nitrogen than their crops need. This practice provides a cushion in case an exceptionally rainy year depletes nitrogen levels in the soil.

He says Pivot Bio’s product doesn’t wash away in the rain, so farmers can use the microbes, rather than excess fertilizer, to protect against nitrogen loss. “They’re not going to willy-nilly cut out 40 to 50 units without having some sort of protection,” he says.

But having that protection doesn’t always translate to an increased yield. Instead of emphasizing yield, Poston points to company data showing that plants fertilized with Pivot Bio’s microbes have 14% more nitrogen than plants grown with conventional practices, which he says is evidence the product is working.

Kaiser, who received funding from Pivot Bio for one of his trials, doesn’t buy that argument. “If you’re a grower, yield is what’s going to pay the bills,” he says.

Tregunno, the Azotic executive, says it’s possible that yields in plots studied by the university researchers were held back by a lack of phosphorus, potassium, or some other nutrient rather than nitrogen. He also says the plots may have been too small and that the best way to measure a microbe’s effect is with large field studies.

Azotic has conducted more than 100 of its own trials and found that its product can help farmers reduce nitrogen use by 27% on average. Similarly, Corteva criticizes the size of the university trials. In an emailed statement, the company notes that it has conducted more than 300 field trials across the US that show its microbe can improve yield.

“If you want to show a difference, you increase the sample size,” Tregunno says. “That’s been our strategy: do as many large-scale field trials as we can.”

Despite the lackluster conclusions from the university research, Emerson Nafziger, a University of Illinois Urbana-Champaign researcher who contributed to the collection of studies, suspects that microbial fertilizers will work in certain areas, such as sandy soils or soils that are susceptible to nitrogen loss because they contain little organic matter.

He says the microbial products may do better when they don’t have to outcompete natural microbes. But his trials on central Illinois’s dark, fertile soils—funded by the Illinois Fertilizer and Chemical Association, a trade organization supporting the agricultural input industry—didn’t find a boost in yield.

“Once we put these things out there, there’s huge numbers of competing microbes,” Nafziger says. “It’s not clear at all that they’ll have a consistent effect.”

New paradigm

Farmers crave consistency. Microbial fertilizer companies aim to provide benefits across a range of soil types, farming practices, and weather conditions, but that’s no simple task for a product that’s alive.

Tregunno says Azotic’s product, called Envita, will provide a benefit on average, but he acknowledges that it won’t work 100% of the time. If customers don’t see a benefit their first year, Azotic offers to provide the product for free the following year so they can try again.

“You can have vastly different weather conditions one year versus the next,” he says. “The crop’s nitrogen demands are going to be very different depending on the year. The effect of Envita is going to be different as well.”

Justin Quandt, a farmer in North Dakota, has tried nitrogen-fixing microbes from Azotic, Corteva, and Pivot Bio, and he thinks certain soils benefit from the products more than others. He’s seen the best response on sandy soils and now applies microbes to almost all his sandy ground.

“I was seeing some spots that were nitrogen deficient between [fertilizer] applications,” he says. “That’s where the Pivot Bio is kicking in. It’s helping me go from application to application.”

While Pivot Bio claims that its products work in nearly all conditions, the company has found that they boost yield the most when a lot of nitrogen has been lost to the environment.

All these data are starting to form a pattern, according to Keith Ehnle, practical farm research lead at Beck’s Hybrids, a seed breeder and retailer that tests agricultural products and compiles the results in a yearly report for customers.

Beck’s has tested products from Azotic, Corteva, and Pivot Bio, and Ehnle says he’s seen the best performance in places where nitrogen is limited. “I’m not trying this on my own farm, where we have heavy, black soils,” he says. “If I farmed some sandy, light soils, . . . I’d run it.”

Kaiser, from the University of Minnesota Twin Cities, has also seen the microbes work. One of his trials in Waseca, Minnesota, found that adding Pivot Bio’s nitrogen-fixing microbes to a cornfield improved yield by 565 kg/ha compared with a field fertilized by synthetic nitrogen alone. But he feels it’s hard to predict a microbe’s performance, and predictability is what farmers need.

The microbes are living organisms that have to grow and outcompete other microbes, Kaiser says. “You don’t know whether that’s going to happen.”

Indeed, living microbes are completely different from the chemical fertilizers they are trying to replace. Pam Marrone, founder of the biologicals industry consultancy Chestnut Bio Advisors, says those differences require a new business model and a different way of measuring success.

She’s critical of the university studies on nitrogen-fixing microbes, in part because she thinks they weren’t large enough to draw accurate conclusions. She also thinks they condemned the products too quickly.

“When a company comes out with a product, it’s version 1.0,” she says. “You can keep improving the product. That’s what you can do with microbes. You can’t do that with chemicals.”

While venture capitalists and software developers are comfortable with this lean start-up model, which favors rapidly testing many prototypes over concentrating design efforts on a single product, she says farmers and agricultural researchers have been slower to accept it. Still, she expects the performance of nitrogen-fixing microbes to continue improving and win over the doubters. “It’s going to be a standard product,” she says.

Microbial fertilizer companies are chipping away at farmers’ skepticism. Pivot Bio says 90% of the customers who use its products return the next year, a number that Marrone says is significant because farmers won’t keep trying a product if there’s no hope for success.

Batie, the farmer from Nebraska, is one of those customers. This is his third year using the product. He’s not coming back because he knows that it works—he’s not convinced of that yet. He’s trying again because this year might be different.

“If you never change anything, you’re going backwards,” he says. “If you’re not willing to try new things, you’re not going to succeed long term.”