Sticky proteins could protect crops more safely than chemical pesticides

By Erik StokstadApr. 25, 2019 , 12:10 PM

Many pesticides have an inherent weakness: The active ingredients don’t adhere well to the plants they protect. After the chemicals are sprayed onto crops, rain can wash them off into the soil and groundwater. Farmers must spray again and hope for dry weather.

Now, researchers have devised a stickier approach to protecting plants, one that could be applied less frequently than chemical pesticides and might be less toxic. They have designed a molecule with two separate chains of amino acids, called peptides. One peptide embeds itself in the waxy surface of a leaf, holding tight in the rain; the other juts out like a spear to attack microbial pests. In a proof of concept published this month in Green Chemistry, lab tests showed the molecules lessened symptoms of soybean rust, a dreaded fungus that causes one of the world’s worst agricultural diseases.

The peptides will face many challenges before they can reach the market. But plant pathologists say they could be a flexible new way to protect crops. “With the current scale of the soybean rust problem, and the rapid evolution of resistance against multiple fungicides, any addition to the toolbox would be welcome,” says Nichola Hawkins at Rothamsted Research in Harpenden, U.K. Ralph Hückelhoven at the Technical University of Munich in Germany also considers the technique promising. “It opens a treasure box of solutions,” he says. “It’s a bit surprising that no one has done this before.”

To make the new pesticide, plant pathologist Uwe Conrath and protein engineer Ulrich Schwaneberg of RWTH Aachen University in Germany teamed up. Schwaneberg specializes in the directed evolution of peptides—adding genes to microbes to produce them, for example, and relying on rounds of mutation and selection to develop strains that produce peptides with improved traits. He has created peptides that attach to slick surfaces such as polypropylene. The team found two that also anchor themselves onto soy leaves.

Attaching a fluorescent protein to the anchor peptides showed that about 60% to 70% of the leaf remained covered with them, even after the plant was doused in a rain simulation chamber. These two anchor peptides also clung well to the leaves of barley, corn, blueberry, and other crops. Schwaneberg says they can be engineered to adhere more or less tightly, as desired.

The next step was to attach an antimicrobial peptide to the anchor. The team chose dermaseptin, a peptide discovered years ago in the skin of tree frogs. Dermaseptin attacks a broad array of microbes, including bacteria and fungi, somehow rupturing their cell membranes. Conrath notes that pathogens are much less likely to evolve resistance—a problem with chemical pesticides—because it is difficult to change the basic structure of cell membranes.

When tested on glass slides, the fused peptide was about as effective against soybean rust spores as chemical fungicides. But in lab tests on plants, the peptide reduced symptoms of rust by only about 30%. “It’s not enough,” says Emilio Montesinos, a plant pathologist and agronomist at the University of Girona in Spain. “If you want to extend these results for crop protection, you need to do much more work.” Conrath thinks a tactic already used by industry for other pesticides could yield more potent peptides: adding chemicals to distribute them evenly across leaves.

He acknowledges that the peptides are only at the beginning of the pesticide development process, which can last a decade and cost $200 million on average. RWTH Aachen has patented the concept, and Conrath and Schwaneberg plan to start a company to pursue deals with large pesticide manufacturers. They will need help lowering the cost of making the peptides. One way—engineering microbes to produce the peptides themselves in industrial vats—can be tricky when the desired protein tends to kill the microbes that make it.

Another question is safety. Dermaseptin would need to be evaluated for its possible toxicity to humans, as well as the accidental harm it could cause to beneficial insects, fungi, or microbes. “It’s broad-spectrum and it’s persistent, and that creates a regulatory concern,” says Roma Gwynn, who runs Rationale, a pesticide consultancy in Duns, U.K.

Studies indicate that dermaseptin does not harm mammalian cells, and any residues could be removed by washing the plant product with enzymes. Microbes would likely break down peptides remaining in the fields, Conrath says.

As for target pathogens, the team is already thinking beyond soybean rust. They have showed that dermaseptin-based peptides can help protect maize from the common fungus Colletotrichum graminicola. They also want to try attach ing the anchor peptide to Bacillus thuringiensis, or Bt, a insect-killing microbial toxin widely used by organic farmers and engineered into transgenic crops.

Before that, however, Conrath and Schwaneberg plan to outfit their anchors with tiny amounts of copper, commonly used by vineyards and organic farms to fight fungi and other pathogens. This fall, with a €1 million grant from Germany’s Federal Ministry of Food and Agriculture, the team will test the approach in vineyards in southern Germany, which could reduce copper spraying and the runoff that contaminates soil. They’re hoping the idea will stick.