optimization and method of microbial fermentation technology

Fermentation is the cell culture technology known and used by people. Fermentation technology is widely used in medicine, food, agriculture, environmental protection and other fields, which makes it play an increasingly important role in the development of national economy.

In order to improve the level of fermentation production, people first consider the selection of bacteria into the construction of genetic engineering, but in fact, the optimization of fermentation process, including the engineering problems in bioreactors, is also very important.

The optimization of fermentation environmental conditions is the most basic requirement in the fermentation process, and also the most important and most difficult technical index. Optimum control of temperature, pH, dissolved oxygen, stirring speed, ammonia ion, metal ion and nutrient concentration varies according to different fermentations.

At the same time, microorganisms may have different requirements on environmental conditions at different stages of growth and different stages of production of metabolites.

Therefore, the temperature, pH, dissolved oxygen and stirring speed should be constantly changed in the bioreactor to always provide the best environmental conditions for the bioreactor, so as to improve the yield of the target product.

In fermentation enlargement experiments, the optimal medium formulation and optimal temperature, pH, dissolved oxygen and other parameters are generally paid much attention to, but the changes of cell metabolic flow are often ignored. 

For example, in the measurement and control of dissolved oxygen concentration, it is concerned with the optimal oxygen concentration or its critical value, and does not pay attention to the oxygen uptake rate of cell metabolism.

When the pH is regulated by ammonia water, the optimal pH value is concerned, but the dynamic changes in the addition of ammonia water and their relationship with other parameters of the fermentation process are not paid attention to, but these changes are very important for the growth and metabolism of cells.

Based on this, Paragon bio company thinks, we must pay high attention to the changes of cell metabolism flow distribution, the cell metabolism bioreactor material flow and material flow changes of correlation, and the growth of cells, as much as possible to offer real value from the growth change analysis, further establish cell growth and bioreactor operating variables and the relationship between the environment variables, in order to effectively control the flow of cell metabolism, optimizing the fermentation process.

The fed-batch fermentation technology can effectively reduce the decrease in mass transfer efficiency, the inhibition of degradation products and the feedback inhibition of substrates caused by the increase of the viscosity of the medium during the fermentation process, and it can well control the direction of metabolism and extend the product synthesis period and Increase the accumulation of metabolites.

The supplement of the required nutrient limit is often used to control the auxotrophic mutant strains to maximize the accumulation of metabolites. This kind of fed-batch technology is the most common in amino acid fermentation, achieving accurate metabolic control.

The application of ultrasound: ultrasound has a strong biological effect. It can be applied to the upper, middle and downstream stages of the fermentation process. 

Its application in the fermentation process can increase the permeability and selectivity of cell membranes, promote enzyme denaturation or secretion, and enhance cell metabolism, thereby shortening the fermentation period, improving biological reaction conditions, and increasing the quality and yield of biological products.

The mechanism of ultrasound is divided into heat, cavitation and mechanical mass transfer. 

Thermal effect is a phenomenon in which energy is continuously absorbed by the medium during the propagation of ultrasonic waves in the medium to increase the temperature of the medium, which can be used for sterilization or inactivation of enzymes. 

Cavitation is when the ultrasonic wave propagates in the medium, the average distance of the molecules in the liquid changes with the vibration of the molecules. When it exceeds the critical molecular distance to maintain the action of liquid, cavitation (cavitation) is formed. 

The cavity can produce instantaneous high temperature and high pressure accompanied by powerful shock waves or ray streams, etc., which is enough to change the cell wall membrane structure and cause material exchange inside and outside the cell. 

The effect of mechanical mass transfer is that when ultrasonic waves propagate in the medium, the medium particles can enter a vibration state, accelerate the mass transfer of the fermentation liquid, and increase the reaction speed of the fermentation process.

Ultrasound can be widely used in biological fermentation engineering. Different frequencies and intensities of ultrasonic waves have different effects on the fermentation process, and should be selected according to the specific fermentation process and use conditions.

Increasing the synthesis of precursors to increase the synthesis of the precursors of the target product or directly adding the precursors is beneficial to the accumulation of a large amount of the target product. 

For example, in the fermentation of amino acids, precursors are usually added to the culture of microorganisms to produce amino acids; in the fermentation of arachidonic acid, the synthesis of precursors is increased by increasing the precursors or enhancing sugar metabolism, All help to increase the production of arachidonic acid.

Removal of the metabolic end products changes the permeability of the cell membrane, and the end products belonging to the feedback control factor are quickly and continuously discharged outside the cell, and the end products are not accumulated to a concentration that can cause feedback adjustment, which can prevent feedback control.

There are many ways to optimize the fermentation process, and they are not isolated, but interconnected. 

In a kind of fermentation, it is often a combination of multiple optimization methods, the purpose of which is to control the fermentation and produce more and better products according to one's own design.