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Synthetic biology technology drives Shanghai's agricultural innovation scene
Released：2024-10-15 Form：Eastern City and Country Daily
In early September this year, at the 2024 Pujiang Innovation Forum co-sponsored by the Ministry of Science and Technology and the Shanghai Municipal People's Government, a participating project on "green manufacturing of RNA biopesticide" won the highest award of "Excellence Award" in the National disruptive Technology Innovation Competition. The award was presented to Professor Tang Xueming, founder of Siyi Technology (Shanghai) Co., LTD., and principal researcher of the School of Agriculture and Biology at Shanghai Jiao Tong University. The award also focused the attention of the participants on the concern of RNA biopesticides.
To understand what RNA biopesticides mean for national agricultural production and food security, we must first understand the future trend of green agricultural development in China. The new round of scientific and technological revolution and industrial revolution are accelerating, and synthetic biology, known as the third biotechnology revolution, has ushered in a period of rapid development of globalization. At present, the state has greatly increased its support for synthetic biology research, and in the "Fourteenth Five-Year Plan for Bioeconomic Development" issued by the National Development and Reform Commission in May 2022, the application of synthetic biology in agriculture, medicine, food and other fields has been repeatedly mentioned. Especially in the field of agriculture, green topics such as energy conservation and emission reduction, disease prevention and control, and improvement of growth efficiency have become the focus. In June this year, the "Implementation Opinions on Accelerating the Innovation of Agricultural Science and Technology in Shanghai" issued by the General Office of the Shanghai Municipal Government also took the application of synthetic biology technology as one of the key directions of the layout of the new track of agricultural science and technology, and gave high expectations for tapping the potential of biological manufacturing and promoting the green development of agriculture.
The promotion of synthetic biology in agricultural science and technology innovation is manifested in many fields such as biological breeding, biological manufacturing, food nutrition and health. In the past two years, with the support of the Municipal Agriculture and Rural Affairs Committee, many scientific and technological innovation projects are aiming at technological innovation and achievement transformation of relevant disciplines, and actively paving the way for the layout of the new track, while some competitive local enterprises and scientific research teams such as Silicon Yi Technology in Shanghai are like dark horses, adding new momentum to the new quality productivity of Shanghai agriculture.
Generally speaking, the research and development cycle of traditional chemical pesticides is long, the cost is high, and the problems such as environmental pollution caused by the use process and crop resistance are difficult to solve, which has a negative impact on the green and sustainable development of agriculture. Tang Xueming said that the "subversive" of RNA biopesticides lies in the way of RNA interference, targeting the key factor mRNA that interferes with the host (insects or germs) to achieve the precise killing of diseases and pests.
Specifically, dsRNA with specific target to the host (insect or pathogen) is prepared by cell factory or cell-free synthesis method, and acts directly on mRNA. When acting, large fragments of dsRNA will be cut several times, and one of them will bind with the target gene once to stimulate the silencing of the target gene. In the natural environment, dsRNA can achieve rapid degradation, and the degraded products can also be used as a plant growth promoter and be re-absorbed by crops, which is not only environmentally friendly but also can promote yield increase.
The advantage of the new technology is that its development cycle is only 3-6 months. At present, the team is creating RNA-loaded pesticides from scratch to further improve the adsorption capacity of pesticides and reduce research and development costs; At the same time, a full-link production process based on AI intelligent algorithm target screening technology platform and dsRNA bioscale synthesis for preparation research and development has been formed.
In China's "14th Five-Year Plan" national pesticide industry development plan, RNA biopesticides are included in the priority development plan for the first time. Internationally, leading agrochemical enterprises such as Monsanto, Bayer, and Syngenta have also laid out their plans earlier, aiming at the key core technologies of RNA biopesticides.
In 2017, when Tang Xueming founded Siyi Technology, he saw the huge potential space for RNA interference technology to be applied to the field of agricultural green prevention and control. It was an area of technology that he continued to focus on and felt comfortable with as a postdoctoral fellow at Yale and a visiting professor at Oxford a decade later. Facts confirmed his judgment, silicon Yi Technology has become China's first RNA biopesticide high-tech enterprises.
However, from the perspective of international and domestic development in related fields, there is still a general lack of product research and development standards, and it is difficult to obtain approval and supervision of new materials. Siyi Technology led the new track, presided over the development of the world's first RNA biopesicide industrialization standards, obtained the first four RNA pesticide "nucleic acid interferon" naming letter issued in China, at present, has obtained 8; He also created the first RNA fungicide in the world and the first RNA insecticide in China.
In Shanghai, in addition to "dark horses" such as Silicon Yi Technology, there are many agricultural innovation enterprises that also aim to promote green agricultural technology innovation with synthetic biology. Located in Chenjia Town, Chongming, the Yangtze River Delta Agricultural Silicon Valley science and technology innovation Incubator Park is accelerating the layout of agricultural emerging industries and future industries. For example, based on the world's leading D2P protein manufacturing technology, Kangma High Yield (Shanghai) Biological Co., Ltd. has developed a protein nutrient solution bioferfertilizer that can replace chemical fertilizers for crops, and has built the world's largest in vitro protein synthesis factory. Shanghai Zhike Yougu Biotechnology Co., Ltd. is also developing RNA pesticides.
Ergothionein is a kind of natural amino acid, which can clear free radicals, and has many physiological functions such as anti-oxidation, anti-aging and anti-radiation. According to Peng Rihe, the relevant person in charge of the project, the synthesis of ergothione in rice seeds has no safety concerns such as human pathogens or microbial toxins, and the bioactive substances in rice seeds are relatively stable, which is expected to make the production of ergothione simple and economic, while increasing the added value of rice.
In fact, such scientific innovation is not just the simple logic of synthesizing nutrients in plants. In the eyes of the research team, rice is likened to a "plant cell factory", and they find the right "plant cell factory" by finding or modifying the plant chassis, so as to achieve complex biosynthesis with its rich enzyme library, various cell compartmentation and its highly developed cell endometrial system.
In China, the commercial production of artemisinin and paclitaxel has become a typical case, proving the important role of suitable plant chassis as a "plant cell factory" in the production of plant-active natural products. In Shanghai, Yao Quanhong's team created β-carotene-rich gold rice, beet red rice, high-content astaxanthin rice, riboflavin rice, folate rice and Vc rice by using synthetic biology technology and rice seeds as the base. Based on Pichia pastoris, some important feed enzyme engineering strains such as phytase, xylanase and β-glucanase for high specific activity and high temperature resistance were created. Using Escherichia coli as chassis, A one-step method was developed to produce Vc, VB2, the natural anticancer substance terrequinone A, the anti-aging substance NMN, the sleep aid substance melatonin, and the engineering strains that completely degraded various organic pollutants.
The achievement of these seemingly complicated results has an important impact on the production of high value-added crops and the improvement of healthy quality of life. At present, the team is promoting the transformation of relevant scientific and technological achievements, which is also an important value in commercial production.
In the past two years, synthetic biology technology has promoted agricultural scientific research innovation, and its visibility has been continuously improved. Under the new situation, the interdisciplinary construction of synthetic biology and agriculture is actively promoted, and universities, research institutes and enterprises are encouraged to carry out industry-university-research collaborative innovation to a greater extent, and through the introduction of interdisciplinary and cross-field experts, a number of top scientists and innovation teams such as biological breeding and biological manufacturing are introduced.
Since the beginning of this year, the landing and dislocation development of industrial parks such as Zhangjiang Seed Valley in Pudong, Chongming's Yangtze River Delta Agricultural Silicon Valley and Fengxian's Shanghai Agricultural Science and Technology Innovation Valley have continued to gain attention, and a number of agricultural enterprises and scientific research teams of biological breeding and biological manufacturing have been introduced as "invisible champions", and their innovative projects have also attracted expectations. Forming a new agricultural industry chain lays a potential foundation.
To understand what RNA biopesticides mean for national agricultural production and food security, we must first understand the future trend of green agricultural development in China. The new round of scientific and technological revolution and industrial revolution are accelerating, and synthetic biology, known as the third biotechnology revolution, has ushered in a period of rapid development of globalization. At present, the state has greatly increased its support for synthetic biology research, and in the "Fourteenth Five-Year Plan for Bioeconomic Development" issued by the National Development and Reform Commission in May 2022, the application of synthetic biology in agriculture, medicine, food and other fields has been repeatedly mentioned. Especially in the field of agriculture, green topics such as energy conservation and emission reduction, disease prevention and control, and improvement of growth efficiency have become the focus. In June this year, the "Implementation Opinions on Accelerating the Innovation of Agricultural Science and Technology in Shanghai" issued by the General Office of the Shanghai Municipal Government also took the application of synthetic biology technology as one of the key directions of the layout of the new track of agricultural science and technology, and gave high expectations for tapping the potential of biological manufacturing and promoting the green development of agriculture.
The promotion of synthetic biology in agricultural science and technology innovation is manifested in many fields such as biological breeding, biological manufacturing, food nutrition and health. In the past two years, with the support of the Municipal Agriculture and Rural Affairs Committee, many scientific and technological innovation projects are aiming at technological innovation and achievement transformation of relevant disciplines, and actively paving the way for the layout of the new track, while some competitive local enterprises and scientific research teams such as Silicon Yi Technology in Shanghai are like dark horses, adding new momentum to the new quality productivity of Shanghai agriculture.
We will accelerate the distribution of bio-green agriculture
Generally speaking, the research and development cycle of traditional chemical pesticides is long, the cost is high, and the problems such as environmental pollution caused by the use process and crop resistance are difficult to solve, which has a negative impact on the green and sustainable development of agriculture. Tang Xueming said that the "subversive" of RNA biopesticides lies in the way of RNA interference, targeting the key factor mRNA that interferes with the host (insects or germs) to achieve the precise killing of diseases and pests.
Specifically, dsRNA with specific target to the host (insect or pathogen) is prepared by cell factory or cell-free synthesis method, and acts directly on mRNA. When acting, large fragments of dsRNA will be cut several times, and one of them will bind with the target gene once to stimulate the silencing of the target gene. In the natural environment, dsRNA can achieve rapid degradation, and the degraded products can also be used as a plant growth promoter and be re-absorbed by crops, which is not only environmentally friendly but also can promote yield increase.
The advantage of the new technology is that its development cycle is only 3-6 months. At present, the team is creating RNA-loaded pesticides from scratch to further improve the adsorption capacity of pesticides and reduce research and development costs; At the same time, a full-link production process based on AI intelligent algorithm target screening technology platform and dsRNA bioscale synthesis for preparation research and development has been formed.
In China's "14th Five-Year Plan" national pesticide industry development plan, RNA biopesticides are included in the priority development plan for the first time. Internationally, leading agrochemical enterprises such as Monsanto, Bayer, and Syngenta have also laid out their plans earlier, aiming at the key core technologies of RNA biopesticides.
In 2017, when Tang Xueming founded Siyi Technology, he saw the huge potential space for RNA interference technology to be applied to the field of agricultural green prevention and control. It was an area of technology that he continued to focus on and felt comfortable with as a postdoctoral fellow at Yale and a visiting professor at Oxford a decade later. Facts confirmed his judgment, silicon Yi Technology has become China's first RNA biopesticide high-tech enterprises.
However, from the perspective of international and domestic development in related fields, there is still a general lack of product research and development standards, and it is difficult to obtain approval and supervision of new materials. Siyi Technology led the new track, presided over the development of the world's first RNA biopesicide industrialization standards, obtained the first four RNA pesticide "nucleic acid interferon" naming letter issued in China, at present, has obtained 8; He also created the first RNA fungicide in the world and the first RNA insecticide in China.
In Shanghai, in addition to "dark horses" such as Silicon Yi Technology, there are many agricultural innovation enterprises that also aim to promote green agricultural technology innovation with synthetic biology. Located in Chenjia Town, Chongming, the Yangtze River Delta Agricultural Silicon Valley science and technology innovation Incubator Park is accelerating the layout of agricultural emerging industries and future industries. For example, based on the world's leading D2P protein manufacturing technology, Kangma High Yield (Shanghai) Biological Co., Ltd. has developed a protein nutrient solution bioferfertilizer that can replace chemical fertilizers for crops, and has built the world's largest in vitro protein synthesis factory. Shanghai Zhike Yougu Biotechnology Co., Ltd. is also developing RNA pesticides.
Find more breakthroughs in agricultural applications
Ergothionein is a kind of natural amino acid, which can clear free radicals, and has many physiological functions such as anti-oxidation, anti-aging and anti-radiation. According to Peng Rihe, the relevant person in charge of the project, the synthesis of ergothione in rice seeds has no safety concerns such as human pathogens or microbial toxins, and the bioactive substances in rice seeds are relatively stable, which is expected to make the production of ergothione simple and economic, while increasing the added value of rice.
In fact, such scientific innovation is not just the simple logic of synthesizing nutrients in plants. In the eyes of the research team, rice is likened to a "plant cell factory", and they find the right "plant cell factory" by finding or modifying the plant chassis, so as to achieve complex biosynthesis with its rich enzyme library, various cell compartmentation and its highly developed cell endometrial system.
In China, the commercial production of artemisinin and paclitaxel has become a typical case, proving the important role of suitable plant chassis as a "plant cell factory" in the production of plant-active natural products. In Shanghai, Yao Quanhong's team created β-carotene-rich gold rice, beet red rice, high-content astaxanthin rice, riboflavin rice, folate rice and Vc rice by using synthetic biology technology and rice seeds as the base. Based on Pichia pastoris, some important feed enzyme engineering strains such as phytase, xylanase and β-glucanase for high specific activity and high temperature resistance were created. Using Escherichia coli as chassis, A one-step method was developed to produce Vc, VB2, the natural anticancer substance terrequinone A, the anti-aging substance NMN, the sleep aid substance melatonin, and the engineering strains that completely degraded various organic pollutants.
The achievement of these seemingly complicated results has an important impact on the production of high value-added crops and the improvement of healthy quality of life. At present, the team is promoting the transformation of relevant scientific and technological achievements, which is also an important value in commercial production.
In the past two years, synthetic biology technology has promoted agricultural scientific research innovation, and its visibility has been continuously improved. Under the new situation, the interdisciplinary construction of synthetic biology and agriculture is actively promoted, and universities, research institutes and enterprises are encouraged to carry out industry-university-research collaborative innovation to a greater extent, and through the introduction of interdisciplinary and cross-field experts, a number of top scientists and innovation teams such as biological breeding and biological manufacturing are introduced.
Since the beginning of this year, the landing and dislocation development of industrial parks such as Zhangjiang Seed Valley in Pudong, Chongming's Yangtze River Delta Agricultural Silicon Valley and Fengxian's Shanghai Agricultural Science and Technology Innovation Valley have continued to gain attention, and a number of agricultural enterprises and scientific research teams of biological breeding and biological manufacturing have been introduced as "invisible champions", and their innovative projects have also attracted expectations. Forming a new agricultural industry chain lays a potential foundation.
