Chemical Week

Biologicals put down roots in ag markets

Interest from ag majors, new gene-editing tools point to bright future

STIMULATING GROWTH: BioConsortia and Mosaic are jointly developing nitrogen-fixing microbial products.

Rebecca Coons

Farmers face the difficult task of feeding more people with fewer tools. Many pesticides aren’t working as well as they used to, fewer new active ingredients are being introduced, and many widely-used products are facing regulatory pressure and deselection. Farmers also often face tradeoffs between maintaining profitability, delivering product in a sustainable way, and meeting increasingly stringent regulatory demands in terms of Maximum Residue Levels (MRLs). Despite early growing pains, biological solutions such as biopesticides and bioyield products are becoming key components of a more diverse toolkit for sustainable agriculture.

“Agriculture is facing challenging times,” says Gaston Salinas, CEO of Botanical Solution Inc. (BSI, Davis, California), a company using a plant tissue platform to produce botanical products for agriculture. “The sector is facing pressure from sustain- ability macro trends while at the same time having to figure out how to feed 9 billion people by the year 2050.”

Interest in biologicals is growing, notably by Big Ag. In October 2020, Syngenta acquired Valagro (Atessa, Italy), a biologicals company with over 700 employees and eight global production sites, for an undisclosed sum. Syngenta expects the biologicals market is set to nearly double in size over the next five years. In a separate deal earlier this month, Novozymes (Copenhagen, Denmark) and FMC announced an agreement to co-develop and commercialize biological enzyme-based crop protection solutions, specifically FMC’s diamide insecticide technology, and a biocontrol solution for Asian Soybean Rust.

Late last year, BioConsortia (Davis, California) and Mosaic Company (Tampa, FL), the largest US producer of potash and phosphate fertilizer, announced a collaboration to develop and launch nitrogen-fixing microbial products for corn, wheat, and other major non-legume row crops.

“Certain microbes and plants have evolved this symbiotic relationship that has been around for millennia for leguminous crops,” says BioConsortia CEO Marcus Meadows-Smith. “But what we’re doing now is using a microbe that will do this for corn, wheat, and other nonlegume crops.”

Because nitrogen fixation is an energy- intensive process, microbes have feedback loops that switch off in the presence of ample nitrogen. BioConsortia applies gene-editing and other natural processes to switch off those feedback loops. The technology can significantly reduce the amount of nitrogen farmers apply to crops, much of which ends up lost to the environment, with detrimental effects.

BioConsortia’s Advanced Microbial Selection (AMS) process enriches the crop microbiome, allowing the company to identify organisms that influence the expression of beneficial traits in plants. “We have achieved high levels of efficacy with our fungicides and nematicides and a higher level of consistency both for those biopesticides and for our biostimulant products,” Mead- ows-Smith says. “We have a number of products moving through the registration pipeline and under evaluation by various Tier 1 and Tier 2 agrochemical and fertilizer companies.”

BSI, meanwhile, has commercialized its first product, Botristop, a broad spectrum biofungicide that prevents and controls Botrytis cinerea. The fungal disease affects high-value crops worldwide and is responsible for hundreds of millions of dollars in losses every year. ABM-01, the active ingredient in the product, is based on native Chilean plant Quillaja saponaria Molina.

“What makes our work so different from others in botanicals is that we have internally developed a platform to produce practically any plant material in our lab to supply key active ingredients,” says Salinas. “Depending on the plant species, sometimes you can address shortfalls in the supply of those materials or, just as importantly, improve quality.”

BSI is also on track to launch an alternative source of production for the vaccine adjuvant, QS-21, also based on ABM-01. QS-21, which improves the efficacy of antigens, has been in commercial vaccines since 2017 and is currently used in one of the latest approved COVID-19 vaccines. However, it’s expected to be in short supply due to high demand and to strict deforestation laws in Chile.

“QS21 has been extracted from the tree bark of Quillaja saponaria Molina for years,” Salinas says. “It’s a tree that takes up to 15 years to grow before it is ready to be harvested. But, amid a global pandemic, you can’t wait to grow trees to get sufficient access to raw materials and produce the compound in high volumes. With just a 500-square-meter facility, we are in a position to serve nearly all these markets need” at a level of consistency that cannot be achieved with traditional cultivation and extraction, he adds.

Another botanicals company, STK bio-ag technologies (Petah Tikva, Israel), has also developed a natural fungicide. Dubbed Timorex Gold, the active ingredient is based on more than 100 compounds in tea tree oil, some of which work synergistically, says vice president of sales Yair Nativ. “The result of these compounds is a product with multiple modes of actions that disrupt the fungal cell membrane and destroy the cell walls.”

The active ingredient also reduces the energy required to build a plant’s defense response. “An attacked plant can divert energy to growth and yield instead of defense processes,” Nativ adds. Timorex Gold is labeled for a wide variety of high value fruit and vegetable crops, including grapes, leafy vegetables, fruiting vegetables, berries, vines, tree nuts, tropicals, and cucurbits, and is registered in 35 countries. “Currently, we are working mainly in the Americas,” Nativ says. “We have distribution agreements all over Latin America, the US, and Canada. We have some business in Europe, but registration there takes a long time. We also have sales in China, Korea, the Philippines, Australia, and New Zealand.”

Growing trust

Ag biologicals have been available for several years but uptake has been slow. Early product offerings were ineffective or difficult to use, and farmers are hesitant to swap out tried and true chemical solutions.

“Farmers were [previously] sold on biologicals and told it would solve all of their problems,” Nativ says, likening some earlier products to snake oil. “Some worked but had low efficacy. Other early had to be very precise in terms of application, or only could be used for a certain disease at a specific time. Ours are very easy to use, but the perception of biologicals is not great. So we have to educate farmers.”

Increased pest resistance, calls for more sustainable farming practices, and regulatory pressure on traditional pesticides are helping incentivize farmers to give biologicals another look. “Younger generations are more open to biologicals, but in the US especially farmers tend to skew older,” Nativ says. “We see more adoption in high-value crops like fruits and vegetables, but use on row crops is growing very slowly. You can also see the differences between countries. For example, Peru, which exports a lot of goods into the EU and US, is adopting biologicals more quickly because they are keen to meet mandated MRLs and be approved for sale. If you go to the US, where farmers are selling their product into the US, adoption is lower.”

Currently, the biopesticides market is about $3.5 billion, and biostimulants are about another $1.5 billion.

“Growth estimates range from 10–15% per annum,” Meadows-Smith adds. The fact that biopesticides use is largely confined to high-value fruit and vegetable crops is limiting market potential. “For row crops, farmers oftentimes found them too clumsy to use or there wasn’t enough of a commercial benefit to justify the switch. Some early biopesticide launches had to be in cold chain, or they needed to be used in a certain timeframe to be effective. What we’re doing with Mosaic is bringing forward row crop microbials that are robust and easy to use.”

To help bridge the trust gap with farmers, STK is offering hybrid biological/chemical products. “We saw early on that penetrating large markets would be difficult,” Nativ says. “Farmers simply wouldn’t believe that a biological works as well as a chemical. So we came up with the idea of mixing a chemical with a biological to make it a bridge for farmers.”

Nativ expects Big Ag interest will help drive some growth. “When we first entered the market, nobody wanted to work with us and we had to go from farmer to farmer,” Nativ says. “And now, ADAMA, Syngenta, Sumitomo, BASF—all the giants of ag—are adding these solutions to their distribution chains. So, things are getting better and farmers have more access to these products. Big Ag companies are definitely eager to distribute biopesticides, acquire biologicals companies, or collaborate with us. We are filling a gap for them.”

Salinas expects BSI’s Botristop distribu- tion deal with Syngenta, signed in 2019, to help accelerate growth for the biofungicide. “Syngenta is our exclusive distributor in the Chilean market, where our product is a key component of a technical recommendation package that combines traditional chemistry with natural products,” Salinas says. Botristop will also soon be registered in a number of key Latin American countries.

“We’re expecting to launch our product in Peru by the second quarter of 2021, and launch in Mexico and California by the end of 2022,” Salinas says. Additional regulatory progress is also expected in the US and European Union during 2021.

“We are about to sell our first million dollars in Chile,” Salinas says. “We expect to hit $30 million in annual sales from Botristop by 2029. We also have an ambitious goal to reach $90 million in sales by the end of 2029 from Botristop as well as four additional products we expect to launch between 2023–2026.”

Going forward, new technologies will accelerate the pace of new product introductions.

“[W]e are already using gene-editing tools for nitrogen- fixing microbes but also to get overexpression of things like fungicidal or nematicidal metabolites,” Meadows-Smith says. “The big difference now is that these tools are very precise; you can change single base pairs within the genome of the microbe and be very targeted around what you’re doing. In the past, it was akin to working in the dark and using a shotgun. You’d have to go through thousands and thousands of iterations and you’d often get unintended consequences, like inserting DNA into an important functional gene that as a result stopped working. Now, they’re much more precise.”