Team:BIT-China/Background


BACKGROUND

Plants and human health

As native Chinese, we may not take medicine or get injections when we have minor illness. Instead, we may choose food therapy. For example, tea and ginger can be boiled in water to treat diarrhea. The pharmacokinetics of food are related to many elements, in plant food, one of the related substances is the plant secondary metabolites.

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Plant secondary metabolites can be divided into four classes: terpenoid, alkaloids, polyphenol and flavonoid. The flavonoid refers to a series of compounds consist of two phenolic hydroxyl benzene ring interconnected through the central three carbon atoms, divided into four classes: flavone, flavonol, flavanone and isoflavone. Flavonoid are found in a wide variety of plants and has potential medicinal value. Flavonoid are also precursors to many drug molecules, such as luteolin. The pharmacological effects of flavonoid mainly include protection of cardiovascular system, antibacterial and antiviral, anti-tumor, antioxidant, analgesic and anti-inflammatory, etc. Therefore, flavonoid are often used in diseases such as hypertension and Inflammation so that they have high medicinal value.

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As a natural edible flavonoid derived from lemon, eriodictyol is a light yellow crystalline powder with rich pharmacological functions such as anti-oxidation, anti-inflammatory and regulating metabolism. It is often used in the treatment of asthma, allergic rhinitis and rheumatism. Moreover, due to the hydroxyl on its B ring, its antioxidant activity is higher than other general flavonoids.

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Because of these special biological functions, flavonoid have attracted more and more attention. Currently, flavonoid are extracted from plants. However, this is a time-consuming process that requires the use of solvents which are not environmentally safe. Although it has been well documented that microorganisms can produce flavonoid compounds, problems remain, especially in converting these microorganisms into efficient microbial cell factories [1]. We designed and modeled a dynamically controllable co-culture biosynthesis system of eriodictyol , which is expected to break through bottlenecks of current biosynthesis and co-culture of flavonoid compounds, and provide a feasible alternative for future research in this field.

Fermentation industry

Microorganisms are one of the important sources of natural pilot drugs. Fermentation industry is a kind of modern biotechnology which combines traditional fermentation technology with modern DNA recombination, cell fusion and so on. Through modern chemical engineering technology, it produces useful substances or is directly used in industrial production. The development of fermentation industry has a long history. It originated from the fermentation industry of alcohol, glycerol and acetone in the 1920s. In the early 1940s, with the discovery of penicillin, the antibiotic fermentation industry gradually rose. After the 1970s, the development of bioengineering technology, made fermentation engineering enter the stage of directional breeding. Since the 1980s, with the penetration and intersection of disciplines, mathematics, dynamics, chemical engineering principles and computer technology have been used in the study of fermentation processes. Since the 1990s, all the parameters of automatic recording and automatic control of fermentation process have been applied to production.

The fermentation products determine the fermentation process and the process determines the equipment, so the fermentation factory basically corresponds to the following five types: microbial fermentation, microbial enzyme fermentation, microbial metabolite fermentation, microbial transformation fermentation, and bioengineering cell fermentation.

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The application of fermentation industry is very wide. In the pharmaceutical industry, traditional fermentation products include antibiotics, vitamins, animal hormones, medicinal amino acids, nucleotides (such as inosine) and so on. Since the 1990s, more than 100 commonly used antibiotics have been produced, such as penicillin, cephalosporins, erythromycin and tetracycline. Some genetic engineering drugs produced by fermentation engineering include growth hormone, recombinant hepatitis B vaccine, some kinds of monoclonal antibody, interleukin-2, anti-hemophilia factor and so on. At present, the main enzyme products are also produced by fermentation industry, including saccharifying enzyme, amylase, protease, cellulase and so on. At the same time, fermentation industry is also widely used in food industry, environmental science, chemical energy and agriculture. It has many advantages, mainly two points: fermentation process is generally carried out at room temperature and atmospheric pressure biochemical reaction, reaction safety, requirements are relatively simple and industrial fermentation compared with other industries, less investment, quick results, can achieve significant economic benefits. Simply put, the fermentation industry can save resources, protect the environment and reduce the cost and price of drugs.

Co-culture

Co-culture is one of the important means of fermentation industry. As early as 1925 Sack it was described that nitrite and filamentous bacteria were co-cultured in silica gel culture medium. Different combinations can form different products, but they have not been paid enough attention to. In recent decades, it has been gradually found that some biochemical processes need more than two microorganisms to carry out, and some substances need to be co-cultured to produce. Therefore, microbial co-culture has become a hot issue in the fields of industry, agriculture, medicine, food and environmental protection, and has become an important method to increase production or discover new substances.

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Modular co-culture is based on co-culture engineering and modular design. The purpose is to effectively manipulate the target biosynthesis pathway in a mixed culture system composed of a variety of microbial strains.[2] It divides the complete biosynthesis pathway into a series of modules and selects different microbial strains to provide hosts for these individual modules, thus realizing the designed complete biosynthesis route. The advantages of this technique are: reducing the metabolic burden of each strain in the culture system can help to improve the overall biological yield and biotransformation performance; different strains can provide a variety of cell environments, which is conducive to the functional expression of genes in different pathways; More flexible balance of biosynthesis between each pathway module.

References

[1]Tom Delmulle . Sofifie L. De Maeseneire . Marjan De Mey(2018)Challenges in the microbial production of flflavonoids

[2]Deyang Xu, Lili Wang, Chunmei Du. Progress in microbial co-culture - A review[J]. Acta Microbiologica Sinica, 2015,55,(9): 1089-1096.