A fermentation medium having a precursor factor and a method for producing the same

Abstract

The application provides a fermentation medium with precursor factors and a production method thereof, adopts soybean cake powder, concentrated cottonseed protein and the like as basic materials, effectively reduces production cost, optimizes combination of precursor substances, and can obviously improve yield of fermentation products. The precursor substances are mixed with modified bentonite and polyvinyl alcohol for granulation, effective combination, the modified bentonite is absorbed water and expanded in the fermentation liquid, the medium substances can be better suspended in the solution, the stratification in the fermentation liquid is avoided, and the fermentation process is better completed; meanwhile, the slow-release agent is added, the rapid utilization process of the readily available component is delayed, the situation that the concentration is too high in the early stage and the concentration is not enough in the later stage is avoided, the quality of the fermentation product is stabilized, and the yield of the fermentation product is improved. The sodium alginate is grafted in the pores of the aminated bentonite, meanwhile, the hydroxyl groups of the sodium alginate are crosslinked, the gel structure is generated in the interlayer and the pores of the bentonite, the precursor substances can be better loaded, and the combination with glycerol and the slow-release agent is better, and the slow-release effect is better and more stable.

Description

Technical Field

[0001] This invention belongs to the field of bio-fermentation, specifically relating to a fermentation medium containing precursor factors and its production method. Background Technology

[0002] my country is a major producer of pharmaceutical raw materials, with antibiotics, amino acids, and vitamins holding significant positions in the global market. my country's annual production of antibiotic raw materials is approximately 50,000 tons, mostly produced through industrial fermentation, requiring a total culture medium demand exceeding 200,000 tons. my country's output of the three major fermented products is approximately 1 million tons, with enzyme preparations such as amylase, protease, cellulase, and saccharifying enzymes all requiring substantial amounts of culture medium. In recent years, the production capacity of amino acids, vitamins, and hyaluronic acid has been continuously expanding, leading to rapid growth in demand for culture media. The market capacity for culture media exceeds 1 million tons, with high-end products accounting for over 100,000 tons.

[0003] However, the quality of culture media has become a major bottleneck in China's bio-fermentation industry. Microbial strain cultivation, culture media production, and fermentation equipment manufacturing are the three most critical technologies in the fermentation industry. Excellent fermentation strains are the internal factor for high fermentation potency, while culture media and equipment are the external factors. Although my country has the world's largest fermentation production capacity, its fermentation technology has consistently lagged behind international advanced levels. Currently, most of the microbial strains used in domestic industrial production are imported from abroad, and their production capacity is relatively close to international levels. After years of development, fermentation equipment manufacturing, except for a few high-precision control devices, has largely reached international standards in terms of the quality of conventional equipment and has already been exported. However, the production technology and product quality of culture media lag significantly behind those of foreign countries.

[0004] With the development of modern biotechnology, our understanding of microbial metabolite synthesis pathways and metabolic regulation has reached the gene and molecular levels. The concept of "metabolic flux" regulation has been applied in industrial microbial fermentation. Adding precursor substances to the fermentation medium allows microorganisms to directly bind them to product molecules during biosynthesis, without significantly altering their own structure. However, the yield of the product is significantly increased by the addition of the precursor, which also facilitates the realization of computer-controlled "metabolic flux" control in industrial production. Precursors refer to certain compounds added to the fermentation medium that can be directly bound to product molecules by microorganisms, with little change in their own structure, and which promote product synthesis. Developed countries have achieved specialization, customization, and high-value production in culture medium research and manufacturing. For example, products like Pharmamedia and Proflo from Southern Oils & Fats in the United States are produced using advanced technology and equipment, based on the needs of microbial growth and the synthesis of microbial metabolites, with clearly defined components and stable, controllable quality indicators.

[0005] Appropriate precursor addition strategies are crucial for high and stable yields in biofermentation. A sufficient supply of precursors can effectively improve fermentation titer; however, excessive precursors can be toxic to the fermenting bacteria, leading to strain poisoning and reduced yield of the target product. Therefore, the timing and concentration of precursor addition will affect the yield. Summary of the Invention

[0006] To address the problems existing in the prior art, this invention proposes a fermentation medium with precursor factors and its production method, addressing the shortcomings of existing culture medium formulations and production technologies, thereby achieving the following objectives:

[0007] 1. By adding optimized combinations of precursor substances, the yield of fermentation products can be significantly increased, and under certain conditions, the flow of cell synthesis metabolites can be controlled, resulting in a significant increase in the yield of target cells.

[0008] 2. The precursor factor of the present invention has a slow-release property, which not only avoids the toxic effects of excessive precursor substances on the strain in stages, but also allows it to be fully utilized by the production strain, effectively improving the fermentation potency.

[0009] To address the above technical problems, one objective of this invention is to provide a fermentation culture medium containing precursor factors, wherein the fermentation culture medium comprises base materials and precursor substances.

[0010] As a preferred technical solution of the present invention, the base material is a combination of two or more of the following: soybean meal powder, concentrated cottonseed protein powder, yeast powder, peanut meal powder, and fish meal.

[0011] As a preferred technical solution of the present invention, the precursor substance is a combination of two or more of the following: sodium propionate, valine, glycine, indole, betaine, 2-hydroxy-4-methylthiobutyric acid, phenylacetic acid, phenethylthioamine, propionic acid, ammonium molybdate, manganese sulfate, zinc sulfate, ferrous sulfate, and potassium chloride.

[0012] As a preferred embodiment of the present invention, the amount of the precursor substance added is 0.005-0.1 wt% of the base material.

[0013] The second objective of this invention is to provide a method for producing a fermentation medium containing precursor factors, comprising the following steps:

[0014] S1, Mix

[0015] Mix the precursor substances evenly, heat to 50-60℃, then add glycerol and mix evenly, then add modified bentonite and continue mixing, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0016] Preferably, the mass ratio of the precursor material: glycerol: modified bentonite: corn syrup powder is 5-10:2-3:10-15:6-8.

[0017] Preferably, the modified bentonite is prepared by:

[0018] S11. Add bentonite to an alkaline solution and sonicate for 1-2 minutes at a frequency of 150-200 kHz. Then, slowly add glacial acetic acid solution while stirring until the pH is adjusted to 5-6. Add aminosilane coupling agent and sonicate at 50-60°C for 90-120 minutes at a frequency of 120-140 kHz. After the reaction is complete, centrifuge and filter, wash with anhydrous ethanol and distilled water respectively, and dry to obtain aminated bentonite.

[0019] S12. Add aminated bentonite and sodium alginate to distilled water and stir for 10-20 min. Heat to 40-50℃, adjust pH to 4-5.5, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide and react for 2-4 h. Then adjust pH to 8-9, add epichlorohydrin and continue the reaction for 2-4 h. After the reaction is complete, filter, soak in anhydrous ethanol for 10-20 min and wash 3-5 times. After drying, the modified bentonite is obtained.

[0020] Furthermore, the alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 8-10 wt% of the alkaline solution and sodium carbonate accounts for 3-5 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 4-7 mol / L, and the dropping rate is 80-120 ml / min.

[0021] Furthermore, the amount of the aminosilane coupling agent added is 1-2 wt% of the bentonite.

[0022] Further, the molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 7-10:2-4:1-1.5:0.3-0.7; the amount of epichlorohydrin added is 5-9 wt% of sodium alginate.

[0023] Adding bentonite to an alkaline solution, using a mixture of sodium hydroxide and sodium carbonate, and adding glacial acetic acid generates bubbles, which helps increase the interlayer pore structure of the bentonite. The amino groups of aminated bentonite react with the carboxyl groups of sodium alginate, causing sodium alginate to be grafted into the pores of the aminated bentonite. At the same time, the hydroxyl groups of sodium alginate crosslink, forming a gel structure in the interlayer and pores of the bentonite, which can better load precursor substances. When combined with glycerol and a sustained-release agent, the sustained-release effect is better.

[0024] S2, Granulation

[0025] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0026] Preferably, the sustained-release agent is a polyvinyl alcohol solution, and the amount added is 2-5 wt% of the precursor mixture.

[0027] Furthermore, the polyvinyl alcohol solution has a mass fraction of 15-20 wt%.

[0028] S3, Broken

[0029] The precursor particles obtained from S2 are crushed to 100-300 mesh to obtain precursor micro powder.

[0030] S4, Production of fermentation medium

[0031] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0032] By adopting the above technical solution, the technical effect achieved by the present invention is as follows:

[0033] 1. Conventional fermentation media typically use expensive organic nitrogen sources such as peptone and fishmeal, resulting in high production costs. This invention uses soybean meal and concentrated cottonseed protein as base materials, effectively reducing production costs. Optimizing the combination of precursor substances significantly increases the yield of fermentation products. The precursor substances are mixed with modified bentonite and polyvinyl alcohol for granulation, ensuring effective binding and maintaining the precursor substances at an appropriate concentration. The modified bentonite absorbs water and swells in the fermentation broth, allowing the media substances to be better suspended in the solution, preventing stratification and thus facilitating a more efficient fermentation process. Simultaneously, a slow-release agent is added to delay the rapid utilization of fast-acting components, preventing excessively high concentrations in the early stages and insufficient concentrations in the later stages, stabilizing the quality of the fermentation products, and increasing the yield.

[0034] 2. Add bentonite to an alkaline solution, using a mixture of sodium hydroxide and sodium carbonate. When glacial acetic acid is added, the reaction between the acetic acid and sodium carbonate produces bubbles, increasing the interlayer pore structure of the bentonite and facilitating the amination treatment within the bentonite. The amino groups of the aminated bentonite react with the carboxyl groups of sodium alginate, causing sodium alginate to be grafted into the pores of the aminated bentonite. Simultaneously, the hydroxyl groups of sodium alginate crosslink, forming a gel structure in the interlayer and pores within the bentonite. This structure can better load precursor substances, resulting in a better and more stable sustained-release effect when combined with glycerol and a sustained-release agent. Detailed Implementation

[0035] The present invention will be further illustrated below with reference to specific embodiments.

[0036] Example 1: A fermentation medium containing precursor factors and its production method

[0037] S1, Mix

[0038] Mix the precursor substances evenly, heat to 58°C, then add glycerol and mix evenly, then add modified bentonite and continue mixing, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0039] The precursor material, glycerol, modified bentonite, and corn syrup powder, are present in a mass ratio of 6:2:14:7.

[0040] The precursor substances are sodium propionate and manganese sulfate in a mass ratio of 2:1.

[0041] The method for preparing the modified bentonite is as follows:

[0042] S11. Add bentonite to an alkaline solution and sonicate for 2 minutes at a frequency of 180 kHz. Then, slowly add glacial acetic acid solution while stirring until the pH is adjusted to 5.5. Add aminosilane coupling agent and sonicate at 55°C for 110 minutes at a frequency of 130 kHz. After the reaction is complete, centrifuge and filter, wash with anhydrous ethanol and distilled water respectively, and dry to obtain aminated bentonite.

[0043] S12. Aminated bentonite and sodium alginate were added to distilled water and stirred for 15 min. The temperature was raised to 45℃, and the pH was adjusted to 5. 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added and reacted for 3 h. Then the pH was adjusted to 8.5, epichlorohydrin was added and the reaction was continued for 4 h. After the reaction was completed, the mixture was filtered, soaked in anhydrous ethanol for 20 min and washed 5 times. After drying, modified bentonite was obtained.

[0044] The alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 9 wt% of the alkaline solution and sodium carbonate accounts for 4 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 6 mol / L and the dropping rate is 100 ml / min.

[0045] The amount of the aminosilane coupling agent added is 1.5 wt% of bentonite.

[0046] The molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 9:3:1.2:0.5; the amount of epichlorohydrin added is 8 wt% of sodium alginate.

[0047] S2, Granulation

[0048] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0049] The sustained-release agent is a polyvinyl alcohol solution, added at 4 wt% of the precursor mixture; the polyvinyl alcohol solution has a mass fraction of 18 wt%.

[0050] S3, Broken

[0051] The precursor particles obtained from S2 are crushed to 200 mesh to obtain precursor micro powder.

[0052] S4, Production of fermentation medium

[0053] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0054] The precursor substance in the precursor powder is 0.05 wt% of the base material; the base material is soybean meal powder, concentrated cottonseed protein powder and yeast powder in a mass ratio of 1:1:1.

[0055] Example 2: A fermentation medium containing precursor factors and its production method

[0056] S1, Mix

[0057] Mix the precursor substances evenly, heat to 50°C, then add glycerol and mix evenly, then add modified bentonite and continue mixing, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0058] The precursor material, glycerol, modified bentonite, and corn syrup powder, are present in a mass ratio of 5:2:10:6.

[0059] The precursor substances are sodium propionate and ammonium molybdate in a mass ratio of 2:1.

[0060] The method for preparing the modified bentonite is as follows:

[0061] S11. Add bentonite to an alkaline solution and sonicate for 1 min at a frequency of 150 kHz. Then, slowly add glacial acetic acid solution while stirring until the pH is adjusted to 5. Add aminosilane coupling agent and sonicate at 50°C for 90 min at a frequency of 120 kHz. After the reaction is complete, centrifuge and filter, wash with anhydrous ethanol and distilled water respectively, and dry to obtain aminated bentonite.

[0062] S12. Add aminated bentonite and sodium alginate to distilled water and stir for 10 min. Heat to 40℃, adjust pH to 4, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide and react for 2 h. Then adjust pH to 8, add epichlorohydrin and continue the reaction for 2 h. After the reaction is completed, filter, soak in anhydrous ethanol for 10 min and wash 3 times. After drying, the modified bentonite is obtained.

[0063] The alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 8 wt% of the alkaline solution and sodium carbonate accounts for 3 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 4 mol / L and the dropping rate is 80 ml / min.

[0064] The amount of the aminosilane coupling agent added is 1 wt% of bentonite.

[0065] The molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 7:2:1:0.3; the amount of epichlorohydrin added is 5 wt% of sodium alginate.

[0066] S2, Granulation

[0067] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0068] The sustained-release agent is a polyvinyl alcohol solution, added at 2 wt% of the precursor mixture; the polyvinyl alcohol solution has a mass fraction of 15 wt%.

[0069] S3, Broken

[0070] The precursor particles obtained from S2 are crushed to 100 mesh to obtain precursor micro powder.

[0071] S4, Production of fermentation medium

[0072] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0073] The precursor substance in the precursor powder is 0.005 wt% of the base material; the base material is soybean meal, concentrated cottonseed protein powder and yeast powder in a mass ratio of 1:1:1.

[0074] Example 3: A fermentation medium containing precursor factors and its production method

[0075] S1, Mix

[0076] Mix the precursor substances evenly, heat to 60°C, then add glycerol and mix evenly, then add modified bentonite and continue mixing, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0077] The precursor material, glycerol, modified bentonite, and corn syrup powder, are present in a mass ratio of 10:3:15:8.

[0078] The precursor substances are sodium propionate and potassium chloride in a mass ratio of 2:1.

[0079] The method for preparing the modified bentonite is as follows:

[0080] S11. Add bentonite to an alkaline solution and sonicate for 2 min at a frequency of 200 kHz. Then, slowly add glacial acetic acid solution while stirring until the pH is adjusted to 6. Add aminosilane coupling agent and sonicate at 60°C for 120 min at a frequency of 140 kHz. After the reaction is complete, centrifuge and filter, wash with anhydrous ethanol and distilled water respectively, and dry to obtain aminated bentonite.

[0081] S12. Aminated bentonite and sodium alginate were added to distilled water and stirred for 20 min. The temperature was raised to 50℃, and the pH was adjusted to 5.5. 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added and reacted for 4 h. Then the pH was adjusted to 9, epichlorohydrin was added and the reaction was continued for 4 h. After the reaction was completed, the mixture was filtered, soaked in anhydrous ethanol for 20 min and washed 5 times. After drying, modified bentonite was obtained.

[0082] The alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 10 wt% of the alkaline solution and sodium carbonate accounts for 5 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 7 mol / L and the dropping rate is 120 ml / min.

[0083] The amount of the aminosilane coupling agent added is 2 wt% of the bentonite.

[0084] The molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 10:4:1.5:0.7; the amount of epichlorohydrin added is 9 wt% of sodium alginate.

[0085] S2, Granulation

[0086] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0087] The sustained-release agent is a polyvinyl alcohol solution, added at 5 wt% of the precursor mixture; the polyvinyl alcohol solution has a mass fraction of 20 wt%.

[0088] S3, Broken

[0089] The precursor particles obtained from S2 are crushed to 300 mesh to obtain precursor micro powder.

[0090] S4, Production of fermentation medium

[0091] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0092] The precursor substance in the precursor powder is 0.1 wt% of the base material; the base material is soybean meal powder, concentrated cottonseed protein powder and yeast powder in a mass ratio of 1:1:1.

[0093] Comparative Example 1

[0094] S1, Mix

[0095] Mix the precursor substances evenly, heat to 58°C, then add glycerol and mix evenly, then add bentonite and continue mixing, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0096] The mass ratio of the precursor material glycerol : bentonite : corn syrup powder is 6:2 :14 :7.

[0097] The precursor substances are sodium propionate and manganese sulfate in a mass ratio of 2:1.

[0098] S2, Granulation

[0099] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0100] The sustained-release agent is a polyvinyl alcohol solution, added at 4 wt% of the precursor mixture; the polyvinyl alcohol solution has a mass fraction of 18 wt%.

[0101] S3, Broken

[0102] The precursor particles obtained from S2 are crushed to 200 mesh to obtain precursor micro powder.

[0103] S4, Production of fermentation medium

[0104] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0105] The precursor substance in the precursor powder is 0.05 wt% of the base material; the base material is soybean meal powder, concentrated cottonseed protein powder and yeast powder in a mass ratio of 1:1:1.

[0106] Comparative Example 2

[0107] S1, Mix

[0108] Mix the precursor substances evenly, heat to 58°C, then add modified bentonite and mix evenly, and finally add corn syrup powder and mix evenly to obtain the precursor mixture.

[0109] The precursor material, modified bentonite, has a mass ratio of 6:14:7 to corn syrup powder.

[0110] The precursor substances are sodium propionate and manganese sulfate in a mass ratio of 2:1.

[0111] The modified bentonite is prepared by:

[0112] S11. Add bentonite to an alkaline solution and sonicate for 2 minutes at a frequency of 180 kHz. Then, slowly add glacial acetic acid solution while stirring until the pH is adjusted to 5.5. Add aminosilane coupling agent and sonicate at 55°C for 110 minutes at a frequency of 130 kHz. After the reaction is complete, centrifuge and filter, wash with anhydrous ethanol and distilled water respectively, and dry to obtain aminated bentonite.

[0113] S12. Aminated bentonite and sodium alginate were added to distilled water and stirred for 15 min. The temperature was raised to 45℃, and the pH was adjusted to 5. 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added and reacted for 3 h. Then the pH was adjusted to 8.5, epichlorohydrin was added and the reaction was continued for 4 h. After the reaction was completed, the mixture was filtered, soaked in anhydrous ethanol for 20 min and washed 5 times. After drying, modified bentonite was obtained.

[0114] The alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 9 wt% of the alkaline solution and sodium carbonate accounts for 4 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 6 mol / L and the dropping rate is 100 ml / min.

[0115] The amount of the aminosilane coupling agent added is 1.5 wt% of bentonite.

[0116] The molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 9:3:1.2:0.5; the amount of epichlorohydrin added is 8 wt% of sodium alginate.

[0117] S2, Granulation

[0118] A small amount of slow-release agent is added to the precursor mixture to wet the material, which is then fed into a granulator to produce precursor granules.

[0119] The sustained-release agent is a polyvinyl alcohol solution, added at 4 wt% of the precursor mixture; the polyvinyl alcohol solution has a mass fraction of 18 wt%.

[0120] S3, Broken

[0121] The precursor particles obtained from S2 are crushed to 200 mesh to obtain precursor micro powder.

[0122] S4, Production of fermentation medium

[0123] The precursor micropowder is added to the base material and mixed thoroughly to prepare the fermentation culture medium.

[0124] The precursor substance in the precursor powder is 0.05 wt% of the base material; the base material is soybean meal powder, concentrated cottonseed protein powder and yeast powder in a mass ratio of 1:1:1.

[0125] The fermentation media prepared in Examples 1-3 and Comparative Examples 1-2 were used to produce abamectin, and the results are shown in Table 1.

[0126] Table 1

[0127]

[0128] Unless otherwise specified, all proportions and percentages mentioned in this invention are mass proportions and mass percentages; all raw materials are commercially available.

[0129] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A fermentation medium containing precursor factors, characterized in that, The fermentation medium includes basic materials and precursor substances; The base material is a combination of two or more of the following: soybean meal powder, concentrated cottonseed protein powder, yeast powder, peanut meal powder, and fish meal. The precursor is a combination of two or more of the following: sodium propionate, valine, glycine, indole, betaine, 2-hydroxy-4-methylthiobutyric acid, phenylacetic acid, phenethylthioamine, propionic acid, ammonium molybdate, manganese sulfate, zinc sulfate, ferrous sulfate, and potassium chloride. The production method of the fermentation medium includes mixing, granulation, crushing, and production of fermentation medium; The mixing process involves uniformly mixing the precursor substances, heating to 50-60°C, then adding glycerol and mixing uniformly, then adding modified bentonite and continuing to mix, and finally adding corn syrup powder and mixing uniformly to obtain the precursor mixture. The precursor material, glycerol, modified bentonite, and corn syrup powder, are present in a mass ratio of 5-10:2-3:10-15:6-8. The modified bentonite is prepared as follows: Bentonite is added to an alkaline solution and ultrasonically dispersed for 1-2 minutes at an ultrasonic frequency of 150-200 kHz. Then, glacial acetic acid solution is slowly added while stirring until the pH is adjusted to 5-6. Then, an aminosilane coupling agent is added and ultrasonically treated at 50-60°C for 90-120 minutes at an ultrasonic frequency of 120-140 kHz. After the reaction is completed, the mixture is centrifuged, filtered, washed with anhydrous ethanol and distilled water respectively, and dried to obtain aminated bentonite. Aminated bentonite and sodium alginate were added to distilled water and stirred for 10-20 minutes. The temperature was raised to 40-50℃, and the pH was adjusted to 4-5.

5. 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added and reacted for 2-4 hours. Then the pH was adjusted to 8-9, epichlorohydrin was added and the reaction was continued for 2-4 hours. After the reaction was completed, the mixture was filtered, soaked in anhydrous ethanol for 10-20 minutes and washed 3-5 times. After drying, modified bentonite was obtained. The granulation process involves adding a small amount of slow-release agent to the precursor mixture, wetting the material, and feeding it into a granulator to produce precursor granules. The sustained-release agent is a polyvinyl alcohol solution, and the amount added is 2-5 wt% of the precursor mixture.

2. The fermentation medium with precursor factors according to claim 1, characterized in that, The amount of the precursor substance added is 0.005-0.1 wt% of the base material.

3. The fermentation medium with precursor factors according to claim 1, characterized in that, The alkaline solution is a mixed solution of sodium hydroxide and sodium carbonate, wherein sodium hydroxide accounts for 8-10 wt% of the alkaline solution and sodium carbonate accounts for 3-5 wt% of the alkaline solution; the concentration of the glacial acetic acid solution is 4-7 mol / L, and the dropping rate is 80-120 ml / min. The amount of the aminosilane coupling agent added is 1-2 wt% of bentonite.

4. The fermentation medium with precursor factors according to claim 1, characterized in that, The molar ratio of the aminated bentonite, sodium alginate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 7-10:2-4:1-1.5:0.3-0.7; the amount of epichlorohydrin added is 5-9 wt% of sodium alginate.

5. A fermentation medium with precursor factors according to claim 1, characterized in that, The crushing process involves crushing the obtained precursor particles to 100-300 mesh to obtain precursor micro powder; the production of the fermentation culture medium involves adding the precursor micro powder to the base materials and mixing them thoroughly to obtain the fermentation culture medium.

Images