Knowledge
Data: 2020-09-08
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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.