The article comes from the precision home, by BiomedLink.
01Synthetic biology opens a new era of "creation"
Synthetic biology, known as the important carrier of the "third biotechnology revolution", is a new interdisciplinary subject in the 21st century. Its essence is to make cells work for human beings and produce desired substances. With this technology, many products we come into contact with in our daily life can be synthesized in the form of biological methods.
For example, the synthesis of artemisinin, whether it is extracted by planting Artemisia annua in large quantities or synthesized by chemical methods, is limited and costly.
In 2005, Amyris company obtained artemisinin by synthetic biology technology, and then obtained artemisinin by chemical synthesis, which greatly improved the output of artemisinin. After cooperating with pharmaceutical giant Sanofi, artemisinin achieved mass production.
According to the data of Industrial Securities, the price of artemisinin dropped from nearly $1,200/kg in 2005 to below $200/kg in two years. It can be seen that the application of synthetic biology can not only improve the product yield, reduce the cost and produce high-value products, but also reduce the damage to the environment caused by planting raw materials or breeding animals, which meets the market requirements of green development.
In recent years, many traditional and emerging enterprises have deployed in the synthetic biology track, and a large number of enterprises in the field of synthetic biology have been born at home and abroad, which have successfully won the favor of the global capital market, which has also expanded the scale of industrial investment and financing.
Thanks to the technical breakthrough and the support of funds and policies, synthetic biology has made a breakthrough in just a few years, and quickly developed its scientific research achievements into practical industrialization, which is widely used in medical, chemical, cosmetics, materials and other fields, and is expected to solve the bottleneck faced by resource problems in these fields.
According to McKinsey’s statistics, it is estimated that by 2025, the economic value of synthetic biology and bio-manufacturing will reach 100 billion dollars, and 60% of the world’s material production in the future can be realized by bio-manufacturing.
02Driving synthetic biologyThe underlying technology of development
Synthetic biotechnology is the application of engineering thinking in the field of biology, which continues the technology based on recombinant DNA, and integrates cell engineering, metabolic engineering and other related technologies, with enzyme catalysis as the core and the goal of creating a new life system.
Key underlying technologies include DNA sequencing, DNA synthesis, DNA editing and gene expression regulation.The rapid progress of the underlying technology and the continuous cost reduction have significantly improved our ability to design and transform DNA, RNA, protein and cell expression forms, and greatly promoted the development of the industrialization of synthetic biology.
DNA sequencing technology
As the core of "reading", the genome sequence of each species is cracked at the DNA level, which reveals the genetic basis of biodiversity in nature and lays a data foundation for finding a powerful "tool" for synthetic biological manufacturing. This technology began in 1970s. At present, the second and third generation sequencing technologies are the mainstream technologies of DNA sequencing, which can realize millions of sequencing reactions at one time.
DNA synthesis technology
Refers to the synthesis of DNA from scratch, which has many unique advantages. Because it is easier to achieve the goal by synthesizing DNA from scratch, and a complete template can be obtained for amplification and modification; The sequences synthesized by artificial optimization are superior to natural sequences, which is helpful for studying genetic mechanism. Some hypotheses can be designed and tested by using these synthetic sequences. In recent years, using the high selectivity and catalytic activity of enzymatic reaction to develop template-independent enzymatic DNA de novo synthesis technology is expected to further improve the efficiency of one-step synthesis, but it is still in its infancy and there are still many problems to be overcome step by step.
Gene editing technology
It is a genetic-related operation technology that modifies DNA sequences at the genome level. The principle is to cut off DNA at the target site by an artificial endonuclease and induce the DNA repair system in the cell to start. At this time, gene editing technology can realize site-specific gene knockout, specific mutation introduction and site-specific modification.
Gene expression regulation
It is one of the core technologies of metabolic engineering and synthetic biology, and plays a vital role in optimizing the efficiency of the synthetic pathway of target products, avoiding the accumulation of excessive metabolic intermediates and improving the productivity of synthetic cells. It is the simplest and most effective way to realize intracellular gene expression by changing the intensity of corresponding gene expression regulatory elements (such as promoters and terminators). At present, corresponding databases have been built for typical model microorganisms to provide different strength and types of regulatory elements. In addition, the regulation of gene expression can also be achieved by using specific proteins or RNA that control global gene expression and adding inducers for dynamic regulation. The existing problems of this technology include insufficient specificity of natural response elements, difficulty in modification and optimization, non-uniform development standards of gene expression regulation tools, and the technology has not been successfully realized from concept verification to industrial large-scale application.
Genome-scale metabolic network model
Relying on massive biological data, establishing a digital cell model at the level of the whole cell system can enable us to describe and simulate the metabolic process of life on the computer. This technology is helpful to understand the organization principle of cell system and the evolution law of life generation, and then predict the influence of various environmental conditions and gene disturbance on cell function, and guide the design of artificial life. The challenge is that it is difficult to obtain accurate kinetic quantitative data for many biological processes at present.
03World-renowned synthetic organismsEnterprise introduction
The industrial chain of synthetic organisms as a whole can be divided into three categories: upstream bottom technology, midstream platform and downstream end products.
upstreamMainly for companies that provide low-level technologies such as DNA synthesis and gene editing;
middle reachesIt is a platform company with strain transformation and automation platform as its core, and provides an efficient and reusable technology platform by integrating corresponding technologies;
lower reachesIt is a product-oriented company that uses synthetic biology technology to produce products needed in various fields.
AmyrisIt is the first Nasdaq listed company in the field of synthetic biology, and also the originator and typical representative of platform companies. After long-term industrial exploration, it has gradually become an influential producer of farnesene and long-chain hydrocarbons. Its strain transformation platform is one of the earliest engineering platforms in the industry, and its functions include DNA design, DNA assembly, DNA quality control, strain transformation, Qualcomm screening, data analysis and amplification experiments. The company’s business includes cleaning and beauty, health care and spices.
GinkgoBioworksIt was listed in May, 2021. Headquartered in the United States, it focuses on the design and production of industrial microorganisms by genetic engineering. With extensive code base, strain engineering, protein engineering and fermentation platform, we can produce and evaluate strains in Qualcomm and customize microorganisms for customers. In 2022, GinkgoBioworks completed the acquisition of Zymergen to integrate its powerful automation and software capabilities, as well as its rich experience in various bioengineering methods, which significantly expanded its synthetic biology platform.
TwistBioscienceFor American listed companies, a new generation of silicon-based DNA synthesis platform with Qualcomm capacity and low cost has been established. This platform can synthesize a large number of high-quality DNA fragments and genes for drug development experiments and clinical diagnosis, and creates a new method for silicon chips to "write" DNA to make synthetic DNA. The main business includes health care-related, pharmaceutical research and industrial chemicals.
SynthegoFounded in 2012, it is a genome engineering company headquartered in Silicon Valley, California. We are building a platform for large-scale scientific research through machine learning, automation and gene editing. The cloud software platform Antha is a computer-aided biological software platform, which can automatically program laboratory equipment, protocols and technological processes. The company’s main business includes using CRISPR gene engineering to transform cells, providing synthetic RNA solutions and providing bioinformatics.
Kaisai biologyFounded in 2000, it is a platform company that has mastered the technologies related to genetic engineering and strain culture in the upstream of the industrial chain, and has completely laid out the whole industrial chain in the biochemical field from genetic engineering, strain culture, biological fermentation, separation and purification, chemical synthesis and application development, and was listed in science and technology innovation board in August 2020. At present, the main products include biological long-chain diacid, bio-based nylon and so on.
Huaheng biologyFounded in 2005, it is a high-tech enterprise with synthetic biotechnology as its core, mainly engaged in the research, development, production and sales of amino acids and other bio-based products, and was listed in science and technology innovation board in April 2021. Products include alanine series products, D- calcium pantothenate and α-arbutin, which can be widely used in many fields such as daily chemicals, medicines and health products, food additives, feeds and so on.
Yikelai biologyFounded in 2015, it is mainly engaged in the research and development of synthetic biological methods and large-scale production. At present, the company’s synthetic biology technology is mainly used in biomedicine, green agriculture, nutrition and health and other fields with good market prospects, and has realized the industrialization of more than 10 products. Products in the biomedical field mainly include sitagliptin intermediates, dulutvir intermediates, etc. Products in the field of green agriculture mainly include: S- cyanohydrin, amino acid oxidoreductase, etc. Nutrition and health products mainly include nicotinamide mononucleotide raw materials.
Blue crystal microorganismFounded at the end of 2016, it is committed to designing, developing, manufacturing and selling new bio-based molecules and materials, including biodegradable materials PHA, regenerative medical materials, new functional ingredients of beauty cosmetics, new food additives, engineering probiotics, etc. It is a leading manufacturer of biological functional molecules and new materials in China.
FinishingYang Yating?
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