Peptide CLE16 is emerging as a key player in the ongoing effort to reduce agriculture’s reliance on chemical fertilizers. For decades, the drive to grow more food has pushed farmers to rely heavily on synthetic nutrients. These substances helped fuel the global agricultural expansion of the late 20th century, but their widespread use has come at a steep environmental cost. Soils are gradually losing their natural richness, water bodies are being polluted by runoff, and fertilizer production itself adds significantly to carbon emissions. Against this backdrop, researchers at the Salk Institute have been investigating a quieter, more organic path—one rooted in the natural biology of plants and fungi.
Their recent findings, published on April 14, 2025, in the Proceedings of the National Academy of Sciences, present an approach centered on enhancing the natural relationship between plants and soil fungi. At the heart of this relationship is CLE16, a small peptide produced by plant roots, which appears to act as a vital messenger in establishing and strengthening plant-fungal partnerships in the soil.
The Fertilizer Dilemma
Since the 1960s, global use of chemical fertilizers has skyrocketed, increasing more than fourfold. These fertilizers have helped feed billions, but they’ve also created a cycle of dependency. The more fertilizers are used, the more soil health declines, forcing farmers to use even more to get the same results.
Producing fertilizers itself is an energy-intensive process, requiring large amounts of fossil fuels. Once applied, they don’t just stay in the fields—excess chemicals often wash into rivers and lakes, damaging aquatic ecosystems, contaminating drinking water, and releasing potent greenhouse gases. In short, while fertilizers have increased food production, they’ve also left a considerable environmental footprint.
Rediscovering a Natural Ally: Fungi
There is, however, an older and less visible system that helps plants access nutrients—one that has been in place for hundreds of millions of years. Arbuscular mycorrhizal fungi are tiny organisms that live in the soil and enter into a symbiotic relationship with plant roots. The fungi provide plants with essential nutrients, especially phosphorus and water, while receiving carbon-rich compounds in return.
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This interaction is made possible through arbuscules, small fungal structures that grow inside root cells and act like nutrient exchange stations. Approximately 80 percent of plant species are capable of forming such partnerships, but modern crop breeding has often pushed this capacity to the background in favor of traits like faster growth and larger harvests.
The Role of CLE16 in Plant-Fungi Communication
Dr. Lena Mueller, an assistant professor at the Salk Institute, and her team focused on understanding how plants communicate with fungi to initiate and maintain these partnerships. Their study zeroed in on Medicago truncatula, a small legume commonly used in plant research. When this plant was grown in the presence of arbuscular mycorrhizal fungi, it began producing high levels of a molecule known as CLE16.
“Many plants evolved to engage in symbiotic relationships with other species, but industrial breeding techniques have dampened many symbiosis traits in our modern-day crops and cemented their dependence on chemical fertilizers. By restoring the natural symbiosis between plant roots and fungi, we could help crops get the nutrients they need without the use of harmful fertilizers. Beyond acting as a biological fertilizer, arbuscular mycorrhizal fungi also add a layer of natural protection to plants that could help us reduce pesticide use, too,” says Mueller. “If we can leverage beneficial fungi and other microbes to help plants establish these symbiotic relationships, we can make our crops, fields, and soils more sustainable and healthier in the long run.”
Lena Mueller, senior author and assistant professor at Salk Institute
This peptide belongs to a family of small signaling molecules that are found across plant species. Previously, most known CLE peptides appeared to suppress symbiosis. CLE16, however, behaved differently—it actually encouraged the relationship.
Sagar Bashyal, a graduate student in Mueller’s lab and the lead author of the study, conducted experiments where he added extra CLE16 to the soil. The response was clear: the fungal arbuscules grew stronger and lived longer. This, in turn, led to an increase in nutrient exchange between the fungi and the plant roots. Essentially, the presence of CLE16 created a positive feedback loop—more symbiosis led to more CLE16 production, which then promoted even more fungal activity.
“We found the first plant CLE peptide to actually favor and promote symbiosis. It’s really exciting from a scientific perspective to get such a surprising new insight into these peptides. It’s a huge step toward achieving sustainable plant-fungi relationships in the field.”
Sagar Bashyal, first author and graduate student in Mueller’s lab
Understanding the Signaling Pathway
To get a better picture of how CLE16 works, the team explored the plant’s internal signaling pathways. They discovered that CLE16 interacts with a protein called CORYNE (CRN), part of the CLAVATA receptor complex. This complex plays a role in how plants respond to environmental cues and stress.
Under stress, plants often become more defensive, making it harder for even helpful fungi to enter the roots. Mueller believes that CLE16, by binding to the CRN-CLAVATA complex, may help reduce this defensive posture, making it easier for beneficial fungi to establish their presence and begin the exchange of nutrients.
Interestingly, the fungi themselves seem to participate in this process in a similar way. The team found that arbuscular mycorrhizal fungi produce their own CLE16-like peptides. These molecules mimic the plant’s CLE16 and can bind to the same receptors, reinforcing the connection between plant and fungus. This imitation allows the fungi to “speak the same language” as the plant, helping to maintain the symbiotic relationship.
From Lab Experiments to Farmland Application
The implications of this discovery are significant. If CLE16 and its fungal mimics can be applied to farmlands, they could help crops form more robust relationships with beneficial fungi, reducing the need for artificial fertilizers. The next steps, Mueller explains, will involve testing whether these peptides work similarly in major crops like soybeans, corn, and wheat.
The researchers are cautiously optimistic. If these findings hold up across a wider range of plants and environmental conditions, it could open the door to a new way of supporting agriculture—one that aligns more closely with natural systems rather than overpowering them.
Mueller also points out another advantage. Beyond nutrient support, these fungi may offer a degree of natural protection against certain pests or diseases, potentially lowering the need for pesticides as well. This dual benefit makes the plant-fungi partnership worth exploring not only for what it can offer in terms of fertility but also for broader ecosystem health.
The Salk Institute’s study adds to a growing body of research that seeks to understand and restore the natural relationships between plants and the organisms around them. While there’s still much to learn, CLE16 represents a tangible piece of the puzzle.
As the world faces the twin challenges of feeding a growing population and protecting the environment, such insights remind us that solutions may not always lie in high-tech fixes. Sometimes, nature’s own mechanisms—quiet, complex, and long-evolved—offer the most resilient answers.
