The effect and control of the concentration and matrix on microbial fermentation.

First, the effect of the concentration of bacteria on fermentation and control the concentration of the bacteria (cells) refers to the content of the bacteria in the unit volume culture liquidIt is an important parameter both in scientific research and in industrial fermentation controlThe size of the bacteria concentration under certain conditions not only reflects the number of bacterial cells but also reflects the differentiation stage whose physiological characteristics of the bacteria cell are not exactly the sameIn the study of fermentation dynamics, it is necessary to use the parameters of bacterial concentration to calculate the ratio growth rate of bacteria and the ratio of product generation rate and other relevant dynamic parameters in order to study the correlation between them to find out their dynamic strain law so the bacteriological concentration is still a basic parameterThe size of the bacteria is closely related to the growth rate of the bacteriaThe growth of bacteria larger than the growth rate is also rapid and slowThe growth rate of the bacteria is different from the growth rate of different kinds of microorganisms related to the type of microorganism and its own genetic characteristicsIts size depends on the complexity of the cell structure and the longer it takes for the cell structure to divideTypical bacteria, yeast, mold and protozoa double times are, and left and right, which indicates the difference in the rate of microbial proliferation of various typesThe growth of bacteria is also closely related to nutrients and environmental conditionsNutrients include various carbon and nitrogen sources and their concentrationsAccording to the equation, the growth rate depends on the concentration of the matrix the matrix the matrix saturation coefficient of various carbon sources is close to the maximum value between the matrix concentration s// when the matrix concentration is close to the growth rateTherefore, there is an upper concentration of nutrients within this limit the growth rate of bacteria than the growth rate increases with the concentration of the matrix but the concentration of the matrix beyond this limit continues to increase but will cause the growth rate to decreaseThis effect is often referred to as matrix inhibitoryThis may be due to high concentrations of matrix formation of high osmotic pressure caused by cell dehydration and inhibit growthThis effect also includes the inhibition of certain compounds such as methanol and phenol to key enzymes or changes in the composition of cell structuresThe upper limit concentration of some nutrients/as follows: glucose 、、。 In the actual production, rich media are commonly used to promote the rapid reproduction of bacteria and bacteria to increase the concentration of dissolved oxygen Therefore, the control of dissolved oxygen in nutrient conditions is very important in the study and control of microbial fermentation The environmental conditions that affect the growth of bacteria include temperature, value, osmosis pressure and moisture activity The size of the bacteria has an important influence on the yield of fermentation products In the ratio-growth rate of the fermentation product is proportional to the bacterial concentration in the formula - the maximum yield product production rate of the fermentation product or the productivity/ The yield of the more concentrated products is also greater, such as amino acids, vitamins and other primary metabolites fermentation is so For secondary metabolites such as antibiotics, the growth rate of controlled bacteria is slightly higher than the level of the most suitable bacteria, the highest productivity of the pro-bacteria However, the high concentration of bacteria will produce other effects on the consumption of nutrients too fast nutrients in the nutrient composition of the obvious change seiswell seismost accumulation may change the metabolic pathway of the bacteria, especially in the culture of oxygen effect is particularly obvious The decrease in dissolved oxygen caused by the increase of bacterial concentration has various effects on fermentation Early yeast fermentation will show the phenomenon of metabolic pathway change, yeast growth stagnation, ethanol production, and the limit of dissolved oxygen in antibiotic fermentation reduces yield As in order to achieve maximum productivity, the concentration of bacteria when the permeone rate and the oxygen transfer rate are balanced, i.e the mass concentration of the bacteria corresponding to the curve of the oxygen transfer rate with the change of the bacteria concentration and the intersection of the oxygen perinatal rate with the change of the bacteria concentration, i.e the concentration of the critical bacteria The rate and volume yield of antibiotics in the bacteria exceeding this concentration will decrease rapidly In addition to having suitable bacterial concentration, we need to try to control the concentration within the appropriate range The growth rate of the bacteria under certain culture conditions is mainly affected by the concentration of the nutritional matrix, so we should rely on regulating the concentration of the media to control the concentration of the bacteria The first step is to determine that there is an appropriate ratio in the base medium formulation to avoid producing too thick or too thin a mass Then through the intermediate supplement to control, such as when the bacteria growth is slow, bacteria concentration is too thin can be added a part of phosphate to promote growth and increase the concentration of bacteria, but adding too much will make the bacteria overgrowth more than the pro-product synthesis to produce inhibition In production, the amount of sugar added in the production process can also be used to control the growth and concentration of bacteria In short, according to different species and products to adopt different methods to achieve the most suitable concentration Second, the effect of matrix on fermentation and its control matrix is the nutrient of cultured microorganisms For fermentation control, the matrix is the material basis for the production of bacterial metabolism, which involves the growth and reproduction of bacteria as well as the formation of metabolites Therefore, the type and concentration of matrix are closely related to fermentation metabolism Therefore, selecting the right matrix and controlling the appropriate concentration is an important method to improve the yield of metabolites According to the equation in batch fermentation, the growth rate of bacteria is a function of matrix concentration In the case of the bacteriological ratio growth rate and matrix concentration are linearly related Under normal conditions, the maximum growth rate of the bacteria can be achieved, however, due to the metabolites and their matrix is too strong, the inhibition effect of the growth rate of the bacteria-to-body growth rate decreased When the glucose concentration is lower than the amount of the amount of the glucose/ does not appear inhibitive effect, when the glucose concentration is higher than the - / most microorganisms can not grow cells appear dehydration phenomenon As far as the formation of the product is concerned, the medium is too rich and sometimes makes the bacteria grow too high viscosity to increase the mass difference bacteria have to spend more energy to maintain their living environment, i.e for non-production energy increases substantially Therefore, controlling the appropriate matrix concentration in batch fermentation is not only beneficial to the growth of the bacteria to the formation of the product The effects of carbon sources, nitrogen sources and inorganic salts on fermentation and their control should be highlighted here The effect of carbon source on fermentation and its control Carbon source is divided into rapid-use carbon source and slow-using carbon source according to the rapid utilization of bacteria The former, such as glucose can be more rapidly involved in metabolism, synthetic bacteria and energy production and the production of decomposition metabolites such as acetone acid, which is conducive to the growth of bacteria but the decomposition of metabolites may have a deterrent effect on the synthesis of products; For example, lactose, sucrose, maltose, corn oil and semi-lactose are the most suitable carbon sources for penicillin, cephalosporin, saline, riboflavin and alkaloid fermentation Therefore, it is important to choose the most suitable carbon source to increase the yield of metabolites The importance of carbon sources was recognized in early studies of penicillin In rapidly utilized glucose media bacteria grow well but penicillin synthesis is small; The effects of sugar on the biosynthesis of penicillin are shown in the figure The slow use of sugar can be seen in the graph as a key factor in penicillin synthesis So slowly dripped glucose instead of lactose to get good results This shows that lactose is a good carbon source for penicillin fermentation, not that it plays a precursor role, but it is slowly used at a rate that is just right for penicillin synthesis requirements other antibiotic fermentation also have a similar situation There are similar conditions in primary metabolism, such as glucose completely inhibiting the production of extomobiotin in the production of co-active vitamin chemical structures and physiological effects similar to natural vitamins compound synthesis It is therefore important to control the use of rapidly used carbon sources that produce deterrent effects In industrial fermentation media, the use of a mixture of carbon sources containing rapid and slow utilization is based on this principle to control the growth of bacteria and the synthesis of products The concentration of carbon sources also has a significant effect Abnormal reproduction of bacteria caused by too rich nutrition has adverse effects on the metabolism of bacteria, synthesis of products and the delivery of oxygen If the rapidly used carbon source used for the result of a deterrent effect is too large, the synthesis of the product will be significantly inhibited; Therefore, it is very important to control the appropriate carbon source concentration For example, in the production of aflatoxin fermentation to maintain the amount of glucose consumption rate / the ratio of bacteria growth rate and penicillin ratio generation rate are zero so must be supplied with the appropriate amount of glucose to maintain the synthesis rate of penicillin Therefore, it is important for industrial fermentation to control the appropriate carbon source concentration The concentration of carbon source control can be controlled by empirical and dynamic method, i.e intermediate feed in fermentation process This is based on different metabolic types to determine the time of sugar supplement, the amount of sugar to supplement, and the way to supplement the sugar The dynamic method is to be controlled according to the dynamic parameters such as the ratio growth rate of the bacteria, the rate of sugar consumption and the ratio generation rate of the product The effect of nitrogen source on fermentation and its control of nitrogen source have the organic nitrogen source and organic nitrogen source They can have a significant effect on the metabolism of bacteria different species and different concentrations can affect the direction and yield of product synthesis Such as glutamate fermentation when the supply is insufficient to promote the formation of alpha ketone diacid; Control the appropriate concentration to maximize glutamate production For example, in the study of the biosynthesis of helical mycomycin found that inorganic ammonium salt is not conducive to the synthesis of helical mycomycin and organic nitrogen sources such as fishmeal are conducive to its formation Nitrogen sources, like carbon sources, have rapidly exploited nitrogen sources and slow-using nitrogen sources The former, such as amino acids such as amino acids of ammonium or ammonium sulfate or ammonium sulfate and corn pulp, while the latter are proteins such as soybean cake powder, peanut cake powder, cotton cake powder, etc The nitrogen sources that each have their own role to be used quickly are easily used by bacteria to promote the growth of bacteria but to regulate the synthesis of certain metabolites, especially the synthesis of certain antibiotics Such as streptomycin in the fermentation of bamboo peach mycin fermentation using the concentration of ammonium salt to promote the growth of bacteria can stimulate mycelium growth but the yield of antibiotics decreased Ammonium salt also regulates the synthesis of column crystal white mycomycin, helical mycomin, Terostar, etc Slow-using nitrogen sources are beneficial to prolong the production period of secondary metabolites and increase the yield of secondary metabolites However, a full amount of input is also easy to promote the growth of bacteria and nutrients prematurely depleted so that the bacteria premature aging and self-soluble and thus shorten the production period of the product In summary, the appropriate nitrogen source and concentration should also be selected for microbial fermentation Fermented media are generally used to use mixed nitrogen sources with fast and slow utilization Such as amino acid fermentation with ammonium sulphate or ammonium acetate and bran hydrolysis, corn syrup; But there is also the use of a single ammonium salt or organic nitrogen source such as soybean cake powder They are being exploited in a similar situation to carbon sources that are used quickly and slowly In order to regulate the growth of bacteria and prevent the germ of the bacteria self-soluble in addition to the nitrogen source in the base medium, but also in the fermentation process to add nitrogen sources to control its concentration There are several methods used in production The supplementing of organic nitrogen sources can be added in the fermentation process to some organic nitrogen sources such as yeast powder, corn syrup, urea, etc which have the effect of regulating growth metabolism Such as the addition of yeast powder in the fermentation of tomycin can improve the fermentation unit, penicillin fermentation in the middle and late sugar utilization slow, bacteria concentration, the phenomenon of decreasing value of urea plus physiological alkaline substances can improve this condition and improve the fermentation unit, amino acid fermentation can also be added as nitrogen source and value regulator urea It is a common method in industry to supplement inorganic nitrogen sources with ammonia or ammonium sulfate Ammonia can be used as both an inorganic nitrogen source and adjustable value In the antibiotic fermentation industry, ammonia is an effective measure to improve fermentation yield, such as other conditions in line with the fermentation unit of antibiotics can be increased by about % But when the value is high and nitrogen is needed to supplement, the physiological acid can be added ammonium sulfate in order to improve the nitrogen content and the adjustment value of the dual purpose Other inorganic nitrogen sources can also be supplemented but are selected according to fermentation control requirements The effect of phosphate on fermentation and its control of phosphorus is necessary for the growth and reproduction of microbial bacteria and is also necessary for anabolic products The maximum average concentration of phosphate allowed for good microbial growth is only /raise to/significantly inhibits the synthesis of phosphates allowed for good synthesis of secondary metabolites In contrast, the concentrations allowed by bacterial growth are much larger than those allowed by secondary metabolite synthesis, with an average difference of several tens to hundreds of times Therefore, controlling the concentration of phosphate is very important for the fermentation of microbial secondary metabolites Phosphate concentration regulates the effect of metabolite synthesis mechanism on primary metabolite synthesis, which is often indirectly produced by promoting the growth of bacteria, which is more complex for secondary metabolites The control of phosphate concentration is generally used in the base medium at an appropriate concentration The requirements for primary metabolism are not as stringent as secondary metabolism For antibiotic fermentation, it is often the use of growth sub-moderate amount of the amount of phosphate concentration is not suitable for the growth of bacteria but does not affect the growth of the amount of phosphate The optimum concentration depends on the characteristics of the bacteria, culture conditions, the composition and origin of the medium, even if the same antibiotic fermentation in different different plants of the phosphate concentration is not consistent or even very different Therefore, the optimum concentration of phosphate seamounts must be determined experimentally in combination with specific local conditions and the raw materials used Phosphorus content in the medium may also cause changes in content due to different formulation methods and sterilization conditions It is reported that the most suitable phosphorus concentration for the growth of tetracycline fermented bacteria using kinymycin streptomycin fermentation bacteria is and the most suitable phosphorus concentration for tetracycline synthesis is Penicillin fermentation is good with % of potassium dihydrophosphate Slow metabolism is sometimes found during fermentation, and phosphates can also be added Intermittent and micro-adding potassium dihydrophosphate in tetracycline fermentation is beneficial to improve the yield of tetracycline In addition to the above main matrix, there are other kiny components that affect fermentation For example, in a carbon-based medium with acetic acid as a carbon source can promote the increase of glutamate production, the spore synthesis of bacillus conobacteria and other secondary metabolites have a special effect must use sufficient concentration stakes to promote the synthesis of bacillus peptides In short, it is very important to control the type of matrix and its dosage in the fermentation process is that the success of fermentation must be carried out in depth according to the characteristics of the production of bacteria and the requirements of the synthesis of individual products in order to achieve good results.