What feeds the world? Biological products emerging in sustainable crop protection
Traditional crop protection products such as pesticides, pesticides, etc. often cause irreversible and serious harm to human health and the environment, which leads to the "desire" of modern agriculture for environmentally friendly new crop protection products, and this gradually increasing "desire" has triggered a large number of investors to flood the market for environmentally friendly sustainable crop protection products.
On April 1, 2022, Edison Information Group released a survey entitled "Feeding the World: Biological Products for Sustainable Crop Protection" for this emerging market, reviewing the development of this field and further discussing a variety of emerging biotechnologies and related biological companies, including RNA interference (RNAi).
01 Crop protection products
The second of the Sustainable Development Goals issued by the United Nations is to eliminate famine worldwide, and achieving this goal requires extremely high food production, but pests and diseases have become the most important threat to food production, and the use of crop protection products has become the most common and effective way to deal with pests and diseases. Among the many crop protection products on the market, new crop protection products that are sustainable, environmentally friendly and developed using biotechnology are attracting more and more attention.
As governments and consumers around the world pay more and more attention to food safety, environmental quality and other issues, the use of traditional pesticides is also increasingly restricted, and governments have legislated to limit the dosage of traditional pesticides used in agricultural production processes, which has led to farmers' need for more environmentally friendly and effective alternatives. In addition, due to the extensive use of organic synthetic pesticides over the years, many pests have gradually adapted and developed resistance, making the effect of these pesticides gradually decline. In contrast, pesticides developed using the latest biotechnology can deal with these problems well, are more environmentally friendly and avoid pest resistance.
This report, which uses glyphosate and nicotine as representatives of traditional herbicides and pesticides, respectively, describes their use over the past few decades and the limitations they have shown in recent years.
Glyphosate has been the most commonly used herbicide for decades, and people around the world apply glyphosate to remove weeds before sowing crops, but in the past decade, studies have shown that it can have many side effects on human health. In 2018, Monsanto was sued for failing to warn consumers that roundup herbicides, which are the main ingredient in glyphosate, cause cancer, but even though this landmark case attracted worldwide attention, glyphosate remains one of the most widely used herbicides worldwide. Although only a few countries and regions have legislation banning the use of glyphosate, it is foreseeable that in the next few years, the regulation of such traditional pesticides will become more and more stringent.
Nicotine is a class of highly effective insecticides that can be applied to a variety of crops, and it can act extensively on the central nervous system of insects, which means that while effectively killing insecticides, it will also kill pollinators indiscriminately, so the European Union and the US Environmental Protection Agency issued regulations restricting the use of nicotine insecticides in 2018 and 2020, respectively.
According to a report released by Mordor Intelligence in January 2022, the global chemicals market for crop protection is valued at $61.3 billion in 2020 and is expected to reach $73.5 billion by 2026, representing a compound annual growth rate of 3.7%, while the global market share of agro-biocontrolants will grow from $3.3 billion in 2019 to $7.4 billion in 2025, according to BID Research's forecasts for December 2020. The compound annual growth rate will reach 14.5%. This shows that the world's demand for crop protection biologics is growing rapidly.
02 Emergence of emerging crop protection technologies
►RNA干扰（RNA interference, RNAi）
RNAi is a biological process used in cells to inhibit protein synthesis, and if used well, it can be used to prevent the survival and reproduction of pests, and there are already two ways to apply this biological process to crop protection.
The first way is to genetically modify crops to make them synthesize RNAi molecules that target pest cells. In 2017, Monsanto was granted a patent for an RNAi-based biological control technology - SmartStax Pro, which can target the killing of a corn root worm (previously the United States needed to spend about $1 billion a year to control it), through smartStax Pro technology, genetically modified corn can produce an RNAi molecule that can inhibit the synthesis of cell membrane-related proteins. This molecule is able to enter corn root worm cells and kill corn root worms. By 2021, China's Ministry of Agriculture and Rural Affairs has also approved the introduction of this technology.
(Note: Monsanto is a multinational agricultural company in the United States that produces its flagship product, Roundup, a world-renowned glyphosate herbicide.) The company is also a leading global producer of genetically modified (GE) seeds. In 2018, Bayer announced the completion of its acquisition of Monsanto. ）
The second method is to industrially produce RNAi molecules before spraying them onto the surface of crops. Monsanto has also been working on this method of killing insects called spray-induced gene silencing (SIGS), and in 2019 Bayer registered with the U.S. Environmental Protection Agency (EPA) to target the killing of a type of tile mite (a pest that harms bees, causing parasitic bees to lose weight, Shortened life) RNAi product , BioDirect, which is also the first EPA approved exogenous RNA component with biopesticide activity.
In addition to Monsanto (Bayer), many other biopesticides are also developing biopesticides that utilize RNAi technology. Companies such as GreenLight Biosciences, Renaissance BioScience and Syngenta are all experimenting with developing RNAi-based insecticides to control Colorado potato beetles. Because the leaves of solanaceous crops such as potatoes contain toxic alkaloids, the beetle gradually evolved a corresponding resistance, which caused nicotine insecticides such as imidacloprid to function. However, the beetle does not have nucleic acid hydrolases in the intestines and cannot digest RNA insecticides, so the use of RNAi-derived biopesticides is effective.
► Activate crop defense mechanisms
Many plant pathogens produce hairpin proteins (a class of proteins widely present in gram-negative plant pathogens), and when crops are invaded by these pathogens, their seeds, roots, and leaves produce receptors that can sense these proteins, stimulating the metabolic activity of the entire plant and promoting the plant's ability to photosynthesis and absorb nutrients. Using this principle, Plant Health Care has developed a patented product, Harpin αβ, which has been widely used in crops such as corn, apples, cherries, blueberries, and sugar cane.
In addition, Plant Health Care has released another short peptide product that mimics the active site of an evoking protein that can promote soybean growth by stimulating the natural defense mechanisms of soybeans. At the same time, the company has also made some modifications to the amino acid sequence of short peptides to make them better induce plants to develop disease resistance, drought resistance or accelerate plant root growth.
(Note: Plant Health Care is a leading supplier of scientifically validated biological products for the agricultural sector.) The company offers products that improve the health, vitality and yield of major field crops such as corn, soybeans, cotton and rice, as well as specialty crops such as fruits and vegetables. As at 13 May 2022, the company had a market capitalisation of £34.7 million. ）
► Simulates pest inhibitors produced by plants themselves
Many plants can produce terpenes with lavender or orange peel odors to protect themselves from insects and pathogens, while attracting pollinators. In order to take advantage of this property of terpenes, Eden Research uses yeast extracts to make degradable sustained-release microcapsules that wrap up the terpenes and release them gradually, and since the microencapsulated terpenes are not subject to pesticide residue control, this product can be used until the harvest of the produce, which helps to reduce the loss of agricultural products in the last few weeks before maturity. So far, Eden Research has launched two of these products, a fungicide and an insecticide for phylloxera.
(Note: Eden Research is an AIM-listed public company with intellectual property and expertise in microencapsules, terpenes and environmental technologies.) The company's main focus is on the use of terpenes to develop a range of low-risk but effective agrochemicals. Eden's products take advantage of the killer effects of natural chemicals produced by plant defense mechanisms, especially the antibacterial properties of terpenes. As of May 13, 2022, the company had a market capitalization of £18.1 million. ）
► Simulates natural bacterial toxins
There are many types of microorganisms in the environment in which plants grow, which together make up the plant microbiome, some of which have inhibitory or killing effects on pests. Lavie Bio uses its parent company Evogene's MicroBoost AI computational predictive biology platform to screen for insecticidal microorganisms that occur naturally in the plant microbiome and then use those microbes to develop pesticides.
(Note: Evogene is a biotechnology company that develops products for the life sciences market by using predictive biology platforms.) It uses computational biology techniques to produce pesticides, agricultural biology and agricultural seed products. As of May 12, 2022, the company's market capitalization was $35.6 million. ）
03 Supplementary reading
► Principles of RNAi technology
The RNAi technology was inspired by the naturally occurring phenomenon of RNA interference. Message RNA (mRNA) molecules are well known to be produced by DNA transcription and can direct protein synthesis. At the same time, another very short microRNA (miRNA) molecule can be produced in the cell, which binds to the target mRNA molecule with complementary sequences, guides the silencing or degradation of the mRNA, which in turn affects protein synthesis and cellular function.
Similar to the naturally occurring RNAi process, synthetic small interference RNAs (siRNAs) can also produce miRNAs with similar effects and achieve inhibition of specific protein expression. In practice, what directly enters the cell is a double-stranded RNA (dsRNA) similar to the mRNA target sequence, which produces siRNA fragments after being processed by the Dixer enzyme, and then binds to proteins with enzymatic function to form a complex, called RNA-induced silencing complex (RISC). RISCs can specifically identify mRNA and guide the degradation of mRNA, enabling the regulation of gene expression at the post-transcriptional level. Using this principle, siRNA sequences can be designed for the essential mRNA in pest cells, and when they enter the pest cells, they can inhibit the synthesis of proteins necessary for their survival, thereby killing insects.
► Company developing RNAi-derived crop protection products
►Greenlight Biosciences has built a cell-free system platform for the production of double-stranded RNA, which facilitates the development of their pesticide products based on RNAi technology. The company expects to launch an RNAi-derived biopesticide for colorado potato beetles in 2022; while the biopesticides against tile mites are already in the field trial phase; in addition, they are also developing a pesticide to control powdery mildew.
The second-generation yeast strains of Renaissance Bioscience have been genetically engineered to produce specific double-stranded RNAs, which is the basis for their development of RNAi-derived pesticide products. At the end of 2021, the company announced that in an independent POC experiment against Colorado potato beetle larvae, their products resulted in a 98.3% mortality rate for larvae and significantly reduced the damage caused by beetles to plants. What's more, experiments have shown that their product can target multiple mRNA targets in beetle cells, so there is no need to worry about the adaptability of beetle evolution, and this product has also entered the field trial stage. The company also has many other patented technologies that have been commercially licensed, such as a yeast cell for alcohol production that is genetically engineered so that it does not produce hydrogen sulfide with a rotten egg flavor during fermentation, thereby significantly improving product quality; and a yeast used to ferment bread, which can reduce the production of the carcinogen acrylamide when fermented at temperatures above 120 ° C. Renaissance Bioscience also has a long-term goal of applying their RNA production and oral drug delivery platform technology to animal and human health products.
►RNAissance is a spin-off of techAccel-backed Donald Danforth Plant Science Center that has developed a spray-on RNA pesticide for the cabbage moth, which estimates that the moth causes more than $4 billion in agricultural losses each year, and the pesticide is still in the field trial stage.
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Author | Li Yuchang
Proofreading | Mo XII Cat that catches butterflies
Edit | Carp
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