The technology of "brewing" artemisinin in fermentor helps human beings realize "creating freedom"

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Using synthetic biotechnology, artemisinin produced by 100 m3 industrial fermentor is equivalent to the output of 50,000 mu of agricultural planting.

If we eat food, meat and oil without land cultivation and animal husbandry, we can get rid of the fate of relying on the weather and the shortage of land resources; If we no longer need carbon-based energy such as oil and natural gas to use gasoline and raw materials for manufacturing various chemical products, we will no longer worry about energy depletion and environmental pollution; If many rare pharmaceutical ingredients are no longer extracted from animals and plants, we will not worry about seemingly impossible things such as species extinction and overfishing. With the rapid development of synthetic biotechnology, all kinds of products we need in the future may be made in the factory workshop like brewing beer.

Recently, the Ministry of Science and Technology approved the construction of the National Synthetic Biotechnology Innovation Center, which will provide strong support for enhancing the innovation ability of enterprises and industries in the field of synthetic biology in China.

Create "artificial creatures" with specific functions

Synthetic biology, as one of the emerging frontier interdisciplinary subjects, was selected as one of the top ten technologies that will change the world in the future by MIT Science and Technology Review in 2004. Wang, deputy director of Tianjin Institute of Industrial Biotechnology, China Academy of Sciences, said that synthetic biology is to design, transform and even recombine targeted organisms with engineering design concepts, so as to create "artificial organisms" that can perform specific functions or are endowed with unnatural functions. It is the "third biological revolution" after the discovery of DNA double helix structure and genome sequencing, which promotes the qualitative change of human life code from "reading" to "writing", enables human beings to overcome the limitations of natural evolution and makes it possible for design to serve human nature.

"Synthetic biology is to redesign and transform life systems at the molecular level," Wang explained, which is very similar to IT technology. If a computer can achieve a certain function, it needs to integrate many components. Genes are equivalent to components with various functions. We design and integrate the genes of the target substance to be synthesized in an engineering way, and then put them into the chassis cells. The redesigned cells are synthetic organisms. Taking the biosynthesis of lycopene as an example, we can first extract all the genes needed for lycopene synthesis from tomatoes, then redesign and combine these genes, then put them into "chassis cells"-Escherichia coli or Saccharomyces cerevisiae to obtain synthetic organisms, and then use glucose as raw material to produce lycopene through a similar process of brewing beer, which is exactly the same as that extracted from tomatoes.

This seemingly simple process involves the cross-integration of biology and chemistry, engineering, computing, bioinformatics and other disciplines, as well as a series of core technologies such as genome sequencing, gene chemical synthesis, gene editing, biological computing and modeling, protein structure analysis, rational design and directional evolution, and the construction and regulation of synthetic pathways.

"From the successful synthesis of the first cell life in 20 10 to the synthesis of functional customized organelles in 20 19, synthetic biology has continuously made major scientific breakthroughs." Wang said that at present, synthetic biotechnology is mainly used in signal transduction, energy conversion, substance synthesis and molecular recognition. Signal transduction can be applied to the intelligent diagnosis and treatment of cancer and diabetes, and can sensitively detect diseases in the body; Energy conversion can be used for artificial photosynthesis. By redesigning the photosynthesis system in plants, the energy absorption and transformation of plants in photosynthesis can be improved, thus shortening the growth cycle of crops and increasing the yield. Material synthesis is to realize the green manufacturing of chemicals, materials and energy by building a synthetic cell factory; Molecular recognition is mainly used in environmental detection, and the sensitivity of detection is improved by enhancing the recognition ability of molecular signals.

Subvert the traditional industrial model

"Traditional chemical synthesis mainly uses carbon-based energy such as oil and natural gas as raw materials. In the production process, a large amount of carbon dioxide and toxic and harmful substances may be produced. Using synthetic biotechnology, we only need yeast, bacteria and so on. As the' chassis' and glucose from corn starch are used as raw materials, we can synthesize all kinds of substances we need, "Wang further introduced. In addition, we can also use plant fibers such as straw as raw materials, and we are even studying the steps of synthesizing substances by plant photosynthesis, and directly use carbon dioxide as raw materials to complete various biosynthesis.

"Therefore, the application of synthetic biotechnology subverts the traditional industrial model in the fields of industry, agriculture, food and medicine, provides solutions to social and economic problems, and creates new economic growth points at the high end of the value chain." Wang said, "At present, synthetic biotechnology is rapidly developing towards practicality and industrialization."

In terms of agricultural products, using microbial cells as cell factories, China has realized the artificial synthesis of ginsenoside, lycopene, breviscapine, gastrodin and other natural products, forming a new manufacturing model and reducing the dependence on land and pollution. Taking gastrodin as an example, the cost of its biosynthesis is 1/200 for plant extraction and 1/2- 1/3 for chemical synthesis, which greatly improves the production efficiency and can completely replace chemical synthesis. Wang said: "There is also salidroside, the main component of Rhodiola, which can only be extracted if it grows in Rhodiola at an altitude of more than 4,000 meters. Through biosynthesis, it can be produced in the factory. "

In petrochemical products, China has created a batch of bio-manufacturing routes for the synthesis of succinic acid, alanine, malic acid and other chemicals, subverting the dependence on traditional resources such as oil and natural gas and the traditional chemical process with high pollution. "Taking alanine as an example, China has taken the lead in building a 10,000-ton L- alanine biosynthesis route in the world. Compared with the chemical synthesis route, the production cost is reduced by 50%, and the wastewater discharge and energy consumption are reduced by 90% and 40% respectively. " Wang said to him.

In the aspect of chemical raw materials, a green new process of hydroxyproline, inositol, levodopa and vitamin B 12 has been realized. Taking inositol as an example, compared with the traditional process, the synthetic biological method reduces the discharge of high phosphorus wastewater by more than 90% and the cost by more than 50%.

In the transformation of traditional industries, the application of green biotechnology, such as bio-textile, bio-papermaking and bio-degumming, has realized carbon dioxide emission reduction, reduced sewage discharge and promoted traditional industries to get rid of the constraints of resources and environment.

Rapid development, but it is urgent to break through the bottleneck

Although the research of synthetic biology has developed rapidly in the world, and the underlying technology, biological system construction and practical technology of synthetic biology have undergone revolutionary changes, it is very important for synthetic biotechnology to realize industrialization, reduce costs and improve its competitiveness with traditional production models. "For example, American synthetic biologists have designed and constructed artificial yeast cells that can produce the antimalarial drug artemisinin. Its technical capacity can realize the production of 100 cubic meter industrial fermentor, which is equivalent to the production of 50,000 mu of agricultural planting, reducing the cost of antimalarial drugs by 90%, which is a major application mode of synthetic biotechnology. " Wang said to him.

"China started late in the field of synthetic biology, but made rapid progress. At present, China's synthetic biology research has ranked second in the world in terms of the number of basic scientific research papers published and the number of technical patent applications. " Wang said that not long ago, two great events in the field of synthetic biology-"2019 International Conference on Metabolic Engineering" and "The 10th China Industrial Biotechnology Development Summit Forum and the 4th Bio-industry Investment Conference" were held in Tianjin. Jens Nelson, one of the founders of metabolic engineering, said that China is playing an increasingly important role in the field of global metabolic engineering. At the same time, the white paper "China Industrial Biotechnology 20 19" was released, which comprehensively summarized the progress and achievements of China's industrial biotechnology in basic research, applied research, technology transformation and industrial development in recent years.

"But compared with the United States, China still has a big gap in basic theory, core system and industrial technology." Wang said frankly that this is mainly manifested in the few original landmark works, and there is no major breakthrough similar to "artificial life" and artemisinin synthesis; The technical method system created by synthetic biological design is not perfect, and there is a gap between standardization and universality of components, which leads to high external dependence of core technologies and key equipment; From basic research to applied technology innovation, it is necessary to better link up, promote the subversive innovation and engineering application of synthetic biotechnology from the perspective of demand increase and core scientific problems, and support the development of bio-industry.

At present, in terms of the mechanism and molecular basis for the establishment of autonomous cell factories, as well as the construction of the underlying core technologies such as DNA synthesis, biological component standardization, gene editing system and synthetic biological rational design, Qualcomm's quantitative and automatic system technology platform construction is still insufficient, and it is urgent to break through the technical bottleneck and occupy the commanding heights of international competition.

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