Synthetic biology is the use of genome sequencing technology, computer simulation technology, bioengineering technology and chemical synthesis technology, etc., under the guidance of engineering ideas, through the synthesis of biological functional elements, devices and systems, cells or living organisms. It is an emerging cross-integration discipline that designs and transforms genetics to have biological functions that meet human needs, and even creates new biological systems. It has formed in many fields such as life science, chemistry, materials science, medicine and health Disruptive technology.
The influence of synthetic biology has risen rapidly since the 21st century. It has been hailed as the key to understanding life and a disruptive technology that will change the future. The use of synthetic biology technology to produce target products has a series of advantages such as high efficiency, economical and environmental friendliness, etc. Therefore, the development and application of this method for a variety of chemicals, new natural drugs, natural products, etc., are in full swing.
The influence of synthetic biology has risen rapidly since the 21st century. It has been hailed as the key to understanding life and a disruptive technology that will change the future. The use of synthetic biology technology to produce target products has a series of advantages such as high efficiency, economical and environmental friendliness, etc. Therefore, the development and application of this method for a variety of chemicals, new natural drugs, natural products, etc., are in full swing.
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Biosynthesis of natural products
• First, conduct research on a known drug whose chemical composition and biosynthetic pathway are known, with the main goal of improving the production process and in a host that is more easily controlled than natural drugs.
• Second, to investigate the existence of unknown compounds that exist in bacterial genomes but have not yet been discovered. The main goal of synthetic biology is to awaken the biosynthesis of cryptic metabolites, facilitate their chemical and functional characterization, and ultimately utilize Production is achieved by known methods.
• Third, screen the "unknowns in unknown", Based on current genome discoveries, such molecules belonging to new chemical classes cannot be discovered for the time being.
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Microbial natural products
Microbial natural products are a major source of innovation in novel biopharmaceuticals
Microbial natural products have always been the main source of new biological drug innovation, and are currently an important resource for the development of clinical antibacterial, antitumor, immunosuppressive and other drugs. With the increasing number of clinical drug-resistant bacteria, the continuous emergence of new pathogenic bacteria and viruses, and the gradual increase in the difficulty of mining natural products with new skeletons, the development of new microbial drugs is facing great challenges.
Traditional microbial drug development is accomplished through large-scale fermentation, cultivation and isolation and extraction of microorganisms. However, many natural strains that can produce valuable active compounds have shortcomings such as difficulty in cultivation, slow growth rate, and low yield, which limit the related industrialization. Production.
As a frontier discipline in the fields of life sciences and medicine in the 21st century, which promotes innovative breakthroughs and interdisciplinary integration, the rise of synthetic biology provides new ideas and methods for solving the dilemma of drug research and development. Under the premise of fully understanding the pathway of microbial drug synthesis, based on the principles of synthetic biology, the dominant microbial strains can be designed and transformed into heterologous high-yielding chassis cells for the production of more active natural products, so as to break through the bottleneck of natural drug production.
Microbial natural products have always been the main source of new biological drug innovation, and are currently an important resource for the development of clinical antibacterial, antitumor, immunosuppressive and other drugs. With the increasing number of clinical drug-resistant bacteria, the continuous emergence of new pathogenic bacteria and viruses, and the gradual increase in the difficulty of mining natural products with new skeletons, the development of new microbial drugs is facing great challenges.
Traditional microbial drug development is accomplished through large-scale fermentation, cultivation and isolation and extraction of microorganisms. However, many natural strains that can produce valuable active compounds have shortcomings such as difficulty in cultivation, slow growth rate, and low yield, which limit the related industrialization. Production.
As a frontier discipline in the fields of life sciences and medicine in the 21st century, which promotes innovative breakthroughs and interdisciplinary integration, the rise of synthetic biology provides new ideas and methods for solving the dilemma of drug research and development. Under the premise of fully understanding the pathway of microbial drug synthesis, based on the principles of synthetic biology, the dominant microbial strains can be designed and transformed into heterologous high-yielding chassis cells for the production of more active natural products, so as to break through the bottleneck of natural drug production.
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High-density fermentation of engineered bacteria
Increasing the culture density of engineered bacteria and increasing the specific productivity of the product
Through the research on the biosynthesis of natural products, find the enzymes needed in the synthesis of natural products, design specific primers to amplify and obtain the full-length fragment of the target DNA, and then use the corresponding restriction endonuclease to digest it , and then insert it into the carrier with DNA ligase to obtain recombinant DNA molecules, and finally introduce the recombinant DNA molecules into recipient cells. and expand recipient cells. Commonly used receptor cells include Escherichia coli, Bacillus subtilis, Agrobacterium, yeast, animal and plant cells, etc.
Through the research on the biosynthesis of natural products, find the enzymes needed in the synthesis of natural products, design specific primers to amplify and obtain the full-length fragment of the target DNA, and then use the corresponding restriction endonuclease to digest it , and then insert it into the carrier with DNA ligase to obtain recombinant DNA molecules, and finally introduce the recombinant DNA molecules into recipient cells. and expand recipient cells. Commonly used receptor cells include Escherichia coli, Bacillus subtilis, Agrobacterium, yeast, animal and plant cells, etc.
Construction of gene expression vectors
This kind of bacteria and cell lines that use genetic engineering to express foreign genes efficiently are generally called "engineered bacteria" (as shown in the picture below). The growth and reproduction of engineering bacteria need to ensure the concentration of various nutrients required for their growth and metabolism, limit the concentration of harmful substances that hinder growth and metabolism, and maintain the appropriate range of parameters such as fermentation temperature, pH value, and dissolved oxygen.
In order to increase the culture density of the engineered bacteria and increase the specific productivity of the product (the output of the product per unit volume per unit time), high-degree fermentation technology is usually used, that is, when the cell population density of microorganisms in liquid culture exceeds that of conventional culture by more than 10 times Culture techniques for growing states.
This technology can not only reduce the culture volume and strengthen the downstream separation and extraction, but also shorten the production cycle and reduce equipment investment, thereby reducing production costs and improving market competitiveness.
The methods of high-density culture mainly include dialysis culture, cell cycle culture, and fed-batch culture. The organic combination of this high-density culture technology and recombinant DNA technology enables large-scale production of natural proteins that could not be obtained in large quantities.
*The content and pictures of the article are organized from the Internet and academic materials. At the same time, the content has been simplified and supplemented to a certain extent. If there are any deficiencies, please point out for correction.
