“Microbial yeast, which doesn’t do what plants do, has been modified with synthetic biology to have the production capacity of plants, and then it can be produced by fermentation.” “Now that we can turn carbon dioxide into glucose molecules, chemical materials and fuels may be able to make sense,” Liu told reporters.
“We don’t have enough arable land to get food from the ocean, which covers 71 percent of the earth’s surface.” Hu Qiang, a professor at the School of Synthetic Biology of Shenzhen University of Technology, said that the “blue granary” during the “13th Five-Year Plan” period was included in the national key research and development plan, but in the past it mainly focused on economic aquaculture water products.
Hu Qiang also came up with an idea: Can the algae widely distributed in the ocean be exploited through synthetic biology technology?
“Algae itself can produce a lot of high-quality products, we hope that by modifying it to make it higher content, higher yield, such as functional oils, including fatty acids, EPA, DHA, etc., we can use synthetic biology methods to increase these oil content of algae.” Hu Qiang told reporters that it can also give algae more “missions” through gene editing, so that it does not produce a certain type or a class of compounds.
China is a big importer of oil, can we use synthetic biotechnology to let more Chinese oil in the “oil bottle”? “We use algae as a bio-based feedstock, and through synthetic biotechnology, we can transform algae into an energy source similar to oil and coal.” “Hu Qiang said.
Indeed, with the development of synthetic biotechnology, many bio-based materials have been industrialized. In 2021, China’s bio-based material production capacity will be 11 million tons (excluding biofuels), accounting for about 31% of the world’s; The output of 7 million tons, the output value of more than 150 billion yuan, accounting for about 2% of the total output value of the chemical industry.
Biodegradable plastics are a typical representative of bio-based materials.
Due to the serious pollution of chemical synthetic plastics, degradable polyester plastic PBS has become a hot new material in recent years, and the limited capacity of raw material succinic acid has been the bottleneck of its development. The two patents of Zhang Xueli, a researcher at Tianjin Institute of Industrial Biotechnology of the Chinese Academy of Sciences, “Genetically engineered Escherichia coli for the production of succinic acid and its construction method and application” and “Recombinant bacteria and construction method for improving the yield of succinic acid” provide a good way for the efficient preparation of succinic acid – the transformation of Escherichia coli and the efficient preparation of biobutyric acid by fermentation method.
Compared with the petrochemical route, the preparation cost of bio-succinic acid is reduced by nearly 20%. Now, we can see biodegradable plastics in packaging materials, disposable tableware and shopping bags, baby diapers, agricultural mulch, textile materials and other fields, and synthetic biotechnology has contributed.
In the field of life and health, the application of synthetic biology is also commendable.
Antibiotics were once the natural enemies of pathogenic bacteria. However, due to the abuse of antibiotics, the rate at which bacteria develop resistance is much higher than the rate at which new antibiotics are developed, resulting in the emergence of “super-resistant bacteria”.
“In 2020, a patient in Shenzhen People’s Hospital was infected with multi-drug resistant Acinetobacter baumannii in his lungs, which means that commonly used antibiotics in clinical practice are basically ineffective. But after phage therapy combined with antibiotics, the multidrug-resistant bacteria were successfully cleared from the patient’s body.
In fact, phage therapy is nothing new. Because phages carry some independent genes, which may bring some side effects, and their complex relationship with bacteria, traditional phage therapy is often limited.
Why was this clinical trial successful?
“We’re using modified phages.” Ma Yingfei, a researcher at the Institute of Synthetic Biology of the Shenzhen Advanced Institute of the Chinese Academy of Sciences, said that, for example, in response to the problem of phages carrying independent genes, phages can be streamlined to remove the dross and select the essence. To solve the problem that the therapeutic effect of phage is not very high, some genes that can enhance bactericidal activity of phage can be integrated into phage genome, so as to give phage better safety and effectiveness.
Ma Yingfei is very optimistic about the future development of synthetic biology, “We often say that the 21st century is the century of biology, subdivision, which synthetic biology will play an important role in promoting and leading.”
“Things” to “creation”, this is the mystery
What makes synthetic biology so amazing? From “thing” to “creation”, this is the secret of synthetic biology.
“The traditional life sciences, it’s top-down, we call things to know.” Liu Chenli made an example, the secret of life is hidden in the box, open the box, the process of opening layer by layer is the process of discovery, which is what life science is doing. “Synthetic life is the other way around. It’s rebuilt from the bottom up, so people put the secrets of life in, and then wrap it up, layer by layer, into a living entity, and see if it works.”
The engineering approach to research is one of the characteristics of synthetic biology.
“Synthetic biology has engineering properties, it is the use of engineering methods to modify life; But it also has scientific properties, because no one has done it, and after the engineering is finished, I don’t know if it can be built, there is scientific ignorance. So synthetic biology is also called engineering biology.” Liu Chenli introduced that design, build, test and learn is the “routine” of engineering research, “we use this” routine “in synthetic biology, is hoping to create more possibilities with engineering methods.”
And that can’t be done without the help of information technology.
“The truth is often very simple, maybe just one sentence, but if you want to summarize a sentence from thousands of data, it requires a strong learning ability, and information technology can play a role.” Ma Yingfei said that now life science has accumulated a considerable amount of data, through information technology can facilitate us to more quickly summarize the mass of data, mining the most important biological information.
“In the early stage, we designed many combinations of genes, put these combinations into the computer, it will output some functional information – whether this combination can produce artemisinin, whether this gene expression… The computer gives you an algorithm, and with that algorithm, we know how to put it together correctly.” Liu Chenli introduced to reporters.
With the help of information technology, the intelligent and automated design and production process can greatly promote the efficiency of synthetic biology research and development. “The production of artemisinin with yeast used to take a decade and a billion dollars per strain, but now it only takes one and a half to two years, and the research and development cost can be reduced by about 90 percent.” Chinese Academy of Sciences, Shenzhen Institute of Advanced Technology research Institute of synthetic biology researcher Si Tong told reporters.
In addition to engineering and computer information science, the development of synthetic biology is inseparable from the integration of life science, physics, chemistry, mathematics, materials science and other disciplines.
“Living glue” is a research achievement in the field of materials synthetic biology by Zhong Chao, a researcher at the Institute of Synthetic Biology of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences. He said that the genetically modified bacteria can become a “smart living glue”, which is not only expected to achieve the automatic repair of undersea oil pipelines, but in the field of medicine, this “glue” can spontaneously find the location of bleeding and plug bleeding wounds.
“Materials synthetic biology is the product of the intersection of materials science and synthetic biology.” Zhong Chao introduced that a large number of materials synthetic biology research is effectively integrating the dynamic characteristics of natural life systems into traditional materials, so that they can achieve self-adaptation, self-healing and self-proliferation characteristics.
Chemistry is also closely related to synthetic biology.
Nylon is a common material in life, but traditional chemical synthesis produces a lot of greenhouse gases and consumes a lot of water and energy. Nowadays, the use of synthetic biotechnology can realize the fermentation synthesis of biological Kinisaurus, greatly reducing energy consumption and pollution. According to the statistics of the Tianjin Institute of Industrial Biotechnology of the Chinese Academy of Sciences, compared with the petrochemical route, the current average energy saving and emission reduction of bio-manufacturing products will reach 30% to 50%, and the future potential will reach 50% to 70%.
“Through the study of biological macromolecules and their internal structures, chemistry provides the toolkit for designing, modifying and synthesizing life, and the development of synthetic biology will also promote the development of chemistry in a green and efficient direction.” Ma Yingfei said.
Qualitative to quantitative, need rational design ability
Although there are rich application scenarios, as a new discipline, the development of synthetic biology, there are also many problems.
“We want to transform and create living systems, but we lack the ability to design them rationally and build them more efficiently.” Liu Chenli made an example, “Give you thousands of blocks, but there is no drawing to tell you what to spell and how to spell.” We currently lack such a ‘blueprint of life.'”
Ma Yingfei agrees: “We still lack the ability to design rationally, so we have to constantly try and error, constantly correct the results of previous designs, and then optimize and improve our designs through the closed loop of design, construction, testing, and learning.” If we can achieve rational design, where what we design is what we want, that could greatly accelerate some of the advances in synthetic biology.”
“The lack of rational design ability is essentially a lack of understanding of the complexity of living organisms.” In Ma Yingfei’s view, due to the extremely high complexity of biological systems, the interaction between gene lines and gene networks is very complex, but at this stage, people do not know enough.
So, under the current conditions, how to obtain “life drawings”? This brings us to the “bio-foundry”.
The “Biofoundry” is an automated facility for biodesign and synthesis. In 2020, the construction of Science City in Guangming District of Shenzhen has started and laid out the major project of “Major scientific and technological infrastructure for synthetic biology Research” (hereinafter referred to as “large facilities”). According to Liu Chenli, a problem in biological experiments and biological research is that the standards are not uniform, and the experimental results made by different laboratories and different people are difficult to compare. The Big Facility is designed to solve this problem by creating high-quality, standardized databases to build large-scale models of life.
“With this model, you can provide a ‘blueprint’ for the design of life.” Liu Chenli said that in the next 20 years, “from qualitative to quantitative, enhance rational design ability” will be an important development direction of synthetic biology.
The purpose of design is for application. But to go from the laboratory to the factory, it is necessary to adapt equipment and processes.
One of Hu’s team’s studies is to use synthetic biology techniques to modify Marine microalgae. He said that there is a big bottleneck in the current research, which is the lack of suitable production equipment and processes.
The modified cells will lose many of their original functions and become more fragile. “Our existing production methods are somewhat primitive and extensive, which cannot meet the needs of cell growth.” Hu Qiang told reporters that the current generalization of market processes and equipment, low efficiency, high energy consumption, restricting the large-scale application of synthetic organisms.
So, how to design a new manufacturing system to adapt to it, make up for the inherent shortcomings of the cell itself, and fully express its advantages?
This brings us to biofabrication. “In fact, biomanufacturing is a carrier, or a reactor or fermenter, which can give full play to the advantages of the modified cells after gene editing, and the shortcomings can be made up by the bioreactor.”
For example, in the synthetic biology of algae research, Hu Qiang suggested “walking on two legs”, on the one hand, on the basis of the current relatively good microalgae chassis cells, continue to build better engineering algae strains; On the other hand, developing the next generation of biofabrication systems.
“We want to be disruptive both in terms of the device and the process.” “When we have both good engineered algae strains and this kind of disruptive bioreactor, I believe it will be fruitful,” Hu said. “I can say that the prospects are very broad.” (Guangming Daily)
(Our reporter Cui Xingyi, our correspondent CAI Yuqi)
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Wisdom Drugs Co., LTD., founded in September 2011, is headquartered in Changzhou Hang Seng Science and Technology Industrial Park. Today, the company’s R&D center is engaged in the process research and development, production, optimization, custom synthesis and technology transfer of API or pharmaceutical intermediates, plant extracts, compounds from laboratory scale to commercial scaleup production, to meet the growing requirements of customers.
Wisdom drugs attaches great importance to research and development and technology investment, and has established long-term strategic cooperation with domestic and foreign science academies, and has a branch in India. The team has developed and cooperated with related preparation projects, and difficult, small market volume, high value-added products, and in strict accordance with the international GMP standard management, products are exported to Europe, America, India, Southeast Asia, the Middle East and South America and other markets. At the same time, the company pays attention to the protection of intellectual property rights, constantly invents and innovates research and development of production processes, circumvent patent and intellectual property problems in the regulatory market, perfect impurity research, and provide customers with a full set of CMC or DMF registration documents.
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