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    Home > Food News > Food Articles > Let the "cofactor" help the industrial biological catalysis

    Let the "cofactor" help the industrial biological catalysis

    • Last Update: 2021-02-26
    • Source: Internet
    • Author: User
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    (left), a professor at Tianjin University in Beijing, is conducting research.
    the basic structure
    functional unit of the organism, the cells show the process of life activity in various chemical reactions. Over the past hundreds of years, scientists have felt that there is still a long way to go before they can truly open the "black box" of cells, even though they have conducted in-depth research into the various ways in which cell metabolism and life processes are expressed, and have allowed these scientific findings to benefit humanity.
    2014, the Chemical Science Department of the National Natural Science Foundation of China established major projects "Research on the metabolic response mechanism and related construction of industrial biocatalysts" and "Single-cell multi-group space-time analysis".
    5 years, scientists have focused on innovation-oriented and demand-driven research around the metabolic process of microbial cells "cofactors" and new methods of fluorescence analysis of space-time resolution of multiple bioactive molecules in a single cell, and actively promoted the industrialization of basic research results.
    the current edition of the Natural Science Foundation will review the research history of these two major projects and show their achievements.as an anaerobic primary nuclear organism, E. coli has a cell wall made up of peptide polysaccharides that contain only simple cytomegi, which is known for causing diarrhea. This micron-sized, simple-structured creature contains unimaginable energy - by importing genes with special functions into E. coli, the compounds we want can be synthesized through material metabolism and cofactor metabolism.
    nearly 20 years, these humble bacteria have played an important role as "cell factories" in industrial bio-catalysis, turning a new page in biological manufacturing.
    recently, the National Natural Science Foundation of China (NSC) major project "the metabolic reaction mechanism of industrial biocatalysts and related construction research" successfully completed the problem. In the five years since the project was implemented, scientists have focused on the cofactor metabolism process at the same time as material metabolism, which not only promotes the scientific understanding of the regulatory mechanism based on cofactor catalyst, but also realizes a number of industrial applications.
    " scientific and technological innovation to come from the industry. Looking back on the course of this major project, Ouyang Pingkai, chief scientist of the project and former president of Nanjing University of Technology and a member of the Chinese Academy of Engineering, told China Science Daily.Relying on the intelligent characteristics of self-replication, self-assembly and self-regulation of microorganisms such as E. coli, yeast and Clostridium difficile acetone, some relatively inexpensive and easy-to-access raw materials can be close to the level of theoretical conversion rate and efficiently synthesize a large number of products needed by people. Scientists call them "industrial biocatalysts".
    21st century, bio-manufacturing lines for commonly used compounds in the chemical industry have been opened, relying mainly on the import of synthetic genes. But more and more scientists are finding that the results of many metabolic pathways are uncertain after the removal or importation of foreign genes, transcription factors, and so on. If only by material metabolism, high efficiency, high yield, high concentration of industrial catalysis process is often difficult to achieve.
    example is the "sugar enzyme" approach. Ouyang Pingkai said. Anaerobic oxidation of sugar, called glycolysis, refers to the process by which glucose or glycogen breaks down into lactic acid under anaerobic or hypoxia conditions while producing a small amount of adenosine triphosphate (ATP). However, the concentration, conversion rate and rate of the product of glycolysis have not been improved, whether individually or jointly reinforced to express the coding genes of key enzymes of glycolysis.
    scientists have found that substances known as cofactors may play an important role.
    factors cannot be ignored. Ouyang Pingkai stressed. Since 2011, he has led a research team from Nanjing University of Technology to discuss scientific issues in the field of industrial bio catalysis with researchers from Beijing University of Chemical Engineering and Tianjin University.
    several seminars, the scientists analyzed the "three low" phenomena of "low conversion rate, low concentration and slow reaction rate" in industrial production. They believe that the lack of scientific awareness of "cofactor metabolism" is hampering the current development of industrial biological catalysis.
    Three scientific issues around the "cofactor", after 3 years of brewing and organization applications, in 2014, Ouyang Pingkai led the scientific research team by the Natural Science Foundation of China major project "industrial biocatalyst metabolic reaction mechanism and related construction research" support.
    , in the view of scientists, this topic is not only facing the major needs of the main battlefield of the national economy, strategic significance, but also a key issue at the forefront of science, which is worthy of in-depth study. face the real problems faced by the industry, return to basic scientific research and become the optimal strategy for scientists to solve problems.
    the implementation of the major project, scientists plan to focus on the realization of "cofactor metabolism and carbon metabolism synergecy mechanism" of scientific understanding. They break down this scientific goal into four subjects, namely, "the construction of a new generation metabolic network model and the design of the optimal pathway", "the mechanism of the role of cofactors in gene transcription and metabolic flow regulation", "the construction and characteristication of the cofactor metabolic regulation system" and "the matching and optimization of material metabolism and cofactor metabolism".
    At the acceptance meeting of the major project not long ago, Professor of The Academy of Pharmaceutical and Life Sciences of Nanjing University of Technology, Should Hanjie, said that logically, the first two topics focus on basic theory and the key scientific issues are "cofactors and the regulatory mechanism of material metabolism";
    it is in such a clear logical framework that scientific research is gradually carried out. Theoretically, the researchers, guided by systems biology, built a new generation of metabolic network models. With this model, researchers can calculate the key nodes of cofactor metabolic regulation and design optimal metabolic pathways.
    , for example, in the metabolism of glucose-producing acid from glutamate, the researchers used this model to work out the three pathways with the highest theoretical yields. "After considering the factors of cofactors in the calculation, it was found that one of the pathway theories had a yield of 87%. " Tan Tianwei, a major project scientist, president of Beijing University of Chemical Engineering and a member of the Chinese Academy of Engineering, said, "This shows that cofactor intervention can change the original thermodynamic system of the metabolism of adjuncid substances to achieve better metabolic pathways." In
    addition, they have established a library of components for the regulation of cofactor metabolism, which has been visited more than 100,000 times since its construction in 2015 and has become an effective tool for studying metabolic pathways.
    , the researchers carried out research on cofactor regeneration, regional regulation, preference regulation and dynamic regulation, and found many new laws. For example, a study of brewing yeast has shown that coupling substances with energy regulation strategies is an important strategy for maximizing and rapidly maximizing the metabolic flow of target products.
    breakthrough of basic theory, the construction of high-efficiency biocatalysts is called out. For example, in traditional butanol fermentation, hydrogen and by-product acetone are produced in large quantities, greatly limiting the atomic economy of the reaction and the total product value. To this end, the "NADH-compensation module" is constructed "without additional manipulation of solvent synthesis pathways such as acetone, which is completely eliminated, which improves the productivity of butanol." Mr Hanjee said.
    2017, this major project is a breakthrough. With the support of this major project, Yuan Yingjin, a professor at Tianjin University's School of Chemical Engineering, published two long articles in Science describing their work in the design and synthesis of two chromosomes of fuse yeast for the total nuclear bio-brewing, laying the foundation for the establishment of a rapid optimization platform for cofactors and carbon metabolism at the genomic level. In March 2018, this achievement was selected as the "Top Ten Advances in Science in China" for 2017.
    addition, they have built biosynthetic pathways for a range of products, effectively synthesized into natural products, biofuels, bio-based chemicals, pharmaceuticals, and fuels. For example, high-yielding lycopene, 7-dehydrogenated cholesterol and fatty alcohol yeast strains have been successfully developed. "In terms of production processes, active ingredients that used to be extracted from plants with very low levels, such as artemisinin extraction, can now be produced using synthetic yeast, reducing environmental damage." Yuan Yingjin pointed out. scientific and technological innovation from the industry, naturally will return to the industry. In the five years since the implementation of this major project, researchers have tried to extend the chain of innovation and push the basic research results into industrial application. "These results provide a theoretical basis and a way to improve atomic economy and space-time efficiency in biological manufacturing by manipulating cofactors in industrial environments, and promote bio-manufacturing of some typical industrial products." Ouyang Pingkai told China Science Daily.
    as a raw material for polyester production, 1,3-propylene glycol has great room for development. At present, DuPont in the United States to cheap glucose as raw materials for biological production technology routes have formed a monopoly.
    tan Tianwei, with the support of the major project, researchers began to explore a new bio-efficient synthesis of 1,3-propylene glycol using glyceel as a raw material. Among them, the key scientific problem is the quantitative relationship between carbon metabolism pathway and 1,3-propylene glycol synthesis.
    this, the researchers developed a new strategy based on cofactors and global optimization of carbon metabolism, resulting in a target product yielding 86 grams per litre, 1.7 times the traditional approach. In 2014, the research team completed an annual production line of 2,000 tons of 1,3-propylene glycol in Tai'an, Shandong Province.
    in bioethanol fermentation, Hanjie led the team based on the theory of cofactor metabolism, from the microbial gene regulation, the construction of a new reaction system, two aspects, designed a new ethanol fermentation process.
    , using this process, the yield rate of small test intermittent fermentation and continuous fermentation reached the highest level reported in the literature. In 2017 and 2018, the research team conducted 30-ton pilot and 320-ton industrial demonstration tests at Cofco Biomass Energy Co., Ltd. in Guangxi. The test showed that the yeast fermentation cycle was shortened by 45% and the average sugar alcohol conversion rate was increased by 3.8%.
    should Hanjie said that it is the regulation of cofactors that changes the state of redox in cells, reduces the amount of by-product glycera, improves cell impermeability, slows cell aging, and accelerates glucose consumption.
    five years, scientists involved in the major project have developed two contrasting images. One is an "eco-sunshine economy" that is large possible throughout the world - through bio-manufacturing, the use of renewable microbial resources to produce energy, chemicals and new materials, to achieve sustainable development of solar-powered industry and agriculture.
    is a microbial cell small visible to the naked eye - a "window" to look at cell metabolism with cofactors has just opened. "Looking forward to learning more details about cofactors working in cells in the future." Ouyang Pingkai said.
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