Introduction to fermentation engineering process and key technology

Fermentation process characteristics

The biggest difference between fermentation and other chemical industries is that it is a chemical reaction carried out by living organisms. Its main features are as follows:

i. Generally speaking, the fermentation process is a biochemical reaction under normal temperature and pressure, which is safe and requires relatively simple conditions.

ii. The raw materials used in fermentation are usually starch, molasses or other agricultural and sideline products, and the reaction can be carried out as long as a small amount of organic and inorganic nitrogen sources are added. Depending on the type of organism, it can selectively use the nutrients it needs. Based on this characteristic, wastewater and waste can be used as raw materials for fermentation to transform biological resources.

iii. The fermentation process is completed by the automatic regulation of the organism, and the reaction has strong specificity, so that relatively single metabolites can be obtained.

iv. Due to the reaction mechanism of the organism itself, it can carry out chemical transformation reactions such as oxidation and reduction of specific parts of some complex compounds in a specialized and highly selective way, and can also produce relatively complex polymer compounds.

v. It is very important to prevent and control the bacterial contamination in the fermentation process. In addition to strict disinfection of equipment and air filtration, the reaction must be carried out under sterile conditions. If the bacteria are contaminated, the production will suffer huge economic losses. If infected with bacteriophage, the fermentation will cause more harm, so the maintenance of sterile conditions is the key to the success of fermentation.

vi. Microbial strains are the fundamental factors for fermentation. Through mutation and strain screening, high-yield strains can be obtained and production equipment can be fully utilized, so that products difficult to produce by conventional methods can be obtained.

vii. Compared with other industries, industrial fermentation has less investment, quick effect, and can achieve significant economic benefits.

Based on the above characteristics, industrial fermentation has attracted more and more attention. Compared with the traditional fermentation technology, the modern fermentation engineering has more advantages in addition to the above characteristics. Such as in addition to the use of microbial cells, can also use animal and plant cells and enzymes, can also use artificial construction of "engineering bacteria" to react; The reaction equipment is not only the conventional fermenter, but a variety of bioreactors instead, automation, high degree of continuity, so that the fermentation level on the original basis to improve and innovation.

Fermentation types

Depending on the characteristics of fermentation and the oxygen requirements of microorganisms, fermentation can be divided into several types:

i. According to fermentation materials, it can be divided into saccharide fermentation, petroleum fermentation, wastewater fermentation and other types.

ii. According to the fermentation products, it can be divided into amino acid fermentation, organic acid fermentation, antibiotic fermentation, alcohol fermentation, vitamin fermentation, etc.

iii. According to the form of fermentation, it is divided into solid fermentation, semi-solid fermentation and liquid fermentation.

iv. According to the fermentation process, it can be divided into batch fermentation, continuous fermentation and flow fermentation.

v. According to the different needs of oxygen in the fermentation process, it can be divided into anaerobic fermentation and ventilation fermentation.

vi. According to metabolites, it is divided into primary metabolite fermentation (alcohol fermentation, amino acid fermentation, organic acid fermentation, etc.) and secondary metabolite fermentation (antibiotic fermentation, pigment fermentation, etc.).

Fermentation process

For any type of fermentation (with the exception of some conversion processes), a defined fermentation process consists of 6 components:

i). The species and the determined seed medium and fermentation medium;

ii). Sterilization of medium, fermenter and auxiliary equipment;

iii). Large-scale, active, pure seed culture production;

iv). Mass production of products under optimal growth conditions of microorganisms in fermenters;

v). product extraction and purification;

vi). Treatment of fermentation waste liquid.

Therefore, it is necessary to carry out continuous research to gradually improve the self-efficiency of the whole fermentation process. Before establishing the fermentation process, the strain should be isolated and modified to synthesize the target product so that the product produced meets the industrial requirements and the yield should be economically valuable. Then determine the requirements of microorganisms in culture, and set up the corresponding equipment. At the same time, the separation and extraction method of the product must be determined. In addition, the overall research plan should also include continuous optimization of microbial species, media and extraction methods during and after fermentation.

Fermentation engineering key technologies

i. Strain selection and breeding technology

Strain selection is based on the requirements of production and the theory of microbial genetic variation. Artificial methods are used to mutate strains, and then various screening methods are used to screen out the target strains that meet the requirements. The purpose of strain breeding is to improve the basic characteristics of the strain, to increase the yield, improve the quality, reduce the cost, reform the technology, convenient management and comprehensive utilization. The basic methods of bacterial breeding include natural breeding, phage resistance breeding, mutagenesis breeding, metabolic engineering breeding, gene directed breeding, genome reorganization and a series of methods.

In the early stage of fermentation engineering and the modern stage of fermentation engineering, wild microorganisms were used as the main body of fermentation. In the modern stage of fermentation, excellent breeding methods are still an important link in the upstream project of fermentation engineering. Firstly, using new screening mechanism and screening identification indicators, we continue to obtain excellent strains from nature. The second is to use genetic engineering, cell engineering technology, combined with molecular biology means, and adopt the principles of metabolic engineering, metabolic regulation, omics, systems biology, etc., to reconstruct the required genetically engineered bacteria or genetic modification of the existing starter strains, so as to obtain excellent strains capable of producing the required fermentation products.

ii. Pure culture technology

Fermentation industry generally uses specific microbial strains for pure culture, so as to achieve the purpose of producing the desired products. Therefore, the fermentation process should be carried out under the condition of no miscellaneous bacteria contamination. Sterile culture of microorganisms is directly related to the success or failure of the production process. If the problem of sterility is not solved well, it will lead to the reduction of the quantity and quality of the required products and the difficulty of post-processing. Heavy will make all the culture medium metamorphic, resulting in tons of media scrap, resulting in serious economic losses, which is more prominent for large-scale production process. In order to ensure the normal progress of the culture process and prevent the occurrence of bacteria, the culture of most microorganisms, including laboratory operation and industrial production, need to carry out strict sterilization. Sterilization of fermentation process involves medium, fermentation equipment and ventilation of fermentation process.

iii. Fermentation process optimization technology

Fermentation process optimization including from microbial cells to macro level optimization of microbial biochemistry, and the cells of physiological regulation, environment, characteristics of reactor, process operating conditions and reactor control complex interactions between simplified as far as possible, and the relationship between these conditions and optimized, make the most suitable for a particular fermentation process system optimization method. This optimization mainly involves four aspects of research content, the first is the study of cell growth process; The second is the stoichiometry of microbial reactions; The third is biological reaction kinetics; The fourth is bioreactor engineering.

iv. Fermentation process amplification technology

In order to achieve the purpose of popularization and transition of laboratory results to industrial scale, it is generally necessary to go through the pilot scale process optimization research. In order to overcome the difficulties, especially for some relatively large scale fermentation products, step by step amplification method is adopted. Fermentation process amplification methods include: FERmenter geometric similarity amplification, oxygen supply capacity similarity amplification, bacteria metabolism similarity amplification, culture conditions similarity amplification, mathematical model simulation and prediction amplification.

v. Downstream separation and purification technology of fermentation engineering

Downstream separation and purification of fermentation products refers to the process of extraction, concentration, purification and finalization of fermentation target products. The importance of separation and purification of fermentation products is mainly reflected in the particularity, complexity and strict requirements of biological products, which leads to the large proportion of separation and purification cost of the whole production cost of fermentation products. The cost of the downstream separation and purification process of fermentation engineering usually accounts for 50%~70% of the production cost, and some even as high as 90%, which often becomes the restriction factor for the implementation of biochemical process instead of chemical process production. Therefore, only by designing reasonable extraction and refining process to improve product quality and reduce production cost can commercial large-scale production of fermented products be realized.

vi. Automatic monitoring and control technology of fermentation process

In a sense, the success or failure of the fermentation process depends entirely on maintaining a controlled and productive environment. The most effective way to achieve this is through direct measurement of various parameter changes and regulation of biological processes. The application of mathematics, chemical principles, electronic computer technology and automatic control devices to the fermentation process, the measurement of biotechnology parameters, the modeling and control of biological process, can carry out efficient control and management of industrial fermentation process and improve production efficiency.