The optimization idea and method of microbial fermentation technology

Fermentation is the first known and used in large-scale cell culture technologyFermentation technology is widely used in medicine, light industry, food, agriculture, environmental protection and other fields, so that this technology in the development of the national economy plays an increasingly important rolein order to improve the level of fermentation production, people first consider the selection of bacteria or the construction of genetic engineeringIn fact, the optimization of fermentation processes, including engineering problems in bioreactors, is also very importantThe optimization of fermentation conditionsfermentation is the most basic requirement in the fermentation process, and it is also the most important and difficult technical index to masterThe optimal control of temperature, pH, dissolved oxygen, stirring speed, ammonia ions, metal ions, nutrient concentrations, etcvaries according to fermentationAt the same time, microorganisms may have different requirements for environmental conditions at different stages of growth and different periods of metabolites for production purposesTherefore, it is necessary to make constant changes in temperature, pH, dissolved oxygen, stirring speed, etcin the bioreactor, and always provide them with the best environmental conditions to improve the yield of the productin fermentation amplification experiments, generally pay attention to the best medium formula and the best temperature, pH, dissolved oxygen and other parameters, but often ignore the changes in cell metabolic flowFor example, when measuring and controlling dissolved oxygen concentration, it is concerned with the optimal oxygen concentration or its critical value, without paying attention to the oxygen intake rate when cell metabolism, when adjusting the pH value with ammonia, but not with regard to the dynamic changes when adding ammonia water and its relationship with other fermentation processes, and these changes are very important to the growth and metabolism of cellsBased on theof , Zhang Siliang of East China University of Technology put forward the idea of "fermentation engineering with cell metabolic flow analysis and control as the core"In his opinion, we must attach great importance to the phenomenon of cell metabolic flow distribution, study the correlation between cell metabolic material flow and bioreactor material flow change, attach great importance to cell growth change, make as much real value analysis as possible from growth changes, and further establish the relationship between cell growth variables and biological reactor operation and environmental variables, in order to effectively control the metabolic flow of cells and realize the optimization of fermentation processfeed batch fermentation technology This technology can effectively reduce the reduction of mass transfer efficiency caused by the increase of the viscosity of the culture, the inhibition of degradation and the feedback inhibition of the substrate, and control the metabolic direction, prolong the asynthetic period of the product and increase the accumulation of metabolism the amount of nutrients required to supplement, commonly used to control the nutrient-defective mutant bacteria, so that metabolites accumulated to the maximum The use of this supplement batch ingest technique in amino acid fermentation is the most common, and accurate metabolic regulation is realized the application of ultrasound has a strong biological effect It can be applied to the upper, middle and lower stages of fermentation process Its application in fermentation process can increase the permeability and selectivity of cell membranes, promote the degeneration or secretion of enzymes, enhance the process of cell metabolism, thus shortening fermentation time, improving biological reaction conditions, and improving the quality and yield of biological products the mechanism of ultrasonic interaction is divided into thermal action, cavitation and mechanical mass transfer Thermal action is an ultrasonic transmission process in the medium, energy is constantly absorbed by the medium and increase the temperature of the medium, can be used for sterilization or enzyme inactivation Caviating is the average distance of molecules in liquids that change with the vibration of molecules when ultrasonic waves propagate in the medium Cavization (empty bubble) is formed when it exceeds the critical molecular spacing that holds the action of the liquid The empty bubble can produce instantaneous high temperature and pressure and is accompanied by a powerful shock wave or ray flow, which is enough to change the cell's wall membrane structure, so that the cell inside and outside the material exchange Mechanical mass transfer is the ultrasonic wave in the medium, can make the media mass into a vibration state, accelerate the quality transmission of fermentation liquid, improve the fermentation process reaction speed ultrasound can be widely used in biofermentation engineering Ultrasonic waves of different frequencies and intensity have different effects on the fermentation process, and should be selected according to the specific fermentation process and conditions of use increase the synthesis of precursors to increase the synthesis of precursors or directly add precursors, are conducive to the mass accumulation of the products of the target For example: in the fermentation of amino acids, usually in the cultivation of microorganisms to add precursors, the production of amino acids, in the fermentation of peanut tetraoleic acid, by increasing precursors or ways to strengthen the metabolism of sugar, increase the synthesis of their precursors, all help to improve the production of peanut tetraoleic acid remove the metabolic end product to change the permeability of the cell membrane, the end product belonging to the feedback control factor is quickly and continuously discharged out of the cell, do not cause the final product to accumulate to the concentration that can cause feedback regulation, that can prevent feedback control there are many ways to optimize fermentation process escmeaned , and they are not isolated, but interconnected In a fermentation, often a combination of various optimization methods, the purpose is to control fermentation, according to their own design, to produce more and better products