An avermectin fermentation production process and avermectin

By adjusting the aeration rate, stirring speed, and temperature in stages, and by adding new fermentation broth, the avermectin fermentation process was optimized, solving the problems of high cost and low yield in existing technologies, and achieving increased avermectin production and resource conservation.

CN115572753BActive Publication Date: 2026-05-26ZANHUANG COUNTRY WANBO BIOLOGY TECH CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZANHUANG COUNTRY WANBO BIOLOGY TECH CO LTD
Filing Date
2022-11-10
Publication Date
2026-05-26

AI Technical Summary

Technical Problem

Existing avermectin fermentation processes are costly, have low yields, and low economic value.

Method used

Based on the different growth stages of Streptomyces avermitilis, the aeration rate, stirring speed, and temperature were adjusted in stages to optimize the fermentation process. In addition, the composition of the culture medium was adjusted to improve the adaptability of the strain to the growth environment and its secondary metabolic capacity.

Benefits of technology

It increased avermectin production, saved resources, reduced energy consumption and costs, and improved economic efficiency.

✦ Generated by Eureka AI based on patent content.

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Abstract

This application relates to the field of pesticide production technology, specifically disclosing a fermentation production process for avermectin and avermectin itself. The avermectin fermentation production process involves inoculating *Streptomyces avermectin* into a culture medium for fermentation. The fermentation process is divided into five stages: 0-20 hours for the adaptation period, 21-80 hours for the growth period, 81-250 hours for the stationary period, and 251-300 hours for the aging period. The aeration rate during the adaptation period is 2000-2500 L / h, during the growth period it is 3000-3200 L / h, during the stationary period it is 2200-2500 L / h, and during the aging period it is 1900-2100 L / h. This avermectin fermentation process can achieve an avermectin yield of 6.89-7.11 g / L, effectively increasing avermectin production. Furthermore, the flexible adjustment of the aeration rate can effectively reduce gas waste, conserve resources, and improve overall economic efficiency.
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Description

Technical Field

[0001] This application relates to the field of pesticide production technology, and more specifically, it relates to an abamectin fermentation production process and abamectin. Background Technology

[0002] Avermectin is a novel biological pesticide that is currently highly favored in the biological pesticide market due to its high efficiency, broad spectrum, and low toxicity. Avermectin is used to control pests such as the diamondback moth, citrus leafminer, rust mites, cotton spider mites, two-spotted spider mites, and cabbage caterpillars. Its unique insecticidal mechanism involves blocking nerve conduction in invertebrates, and its effects are long-lasting. Furthermore, it decomposes easily in water and soil, without polluting the environment. Therefore, it is a biological pesticide with great development potential.

[0003] Avermectin is produced by deep fermentation of Streptomyces avermectin. In the current avermectin fermentation process, Streptomyces avermectin is fermented in a culture medium containing starch, soybean meal, yeast powder, etc., with a cycle of about 300 hours. The temperature is controlled at 27-28℃, the aeration rate is 2800-3000L / h, and the stirring speed is 130r / min.

[0004] Regarding the aforementioned technologies, the applicant believes that the costs are high, the yield of avermectin is low, and the overall economic value is low. Summary of the Invention

[0005] In order to reduce costs and increase avermectin production, thereby improving overall economic value, this application provides an avermectin fermentation production process and avermectin.

[0006] Firstly, this application provides a fermentation production process for avermectin, employing the following technical solution:

[0007] An abamectin fermentation production process involves inoculating Streptomyces avermectin into a culture medium for fermentation. The fermentation process is divided into five stages: 0-20 hours as the adaptation period, 21-80 hours as the growth period, 81-250 hours as the stationary period, and 251-300 hours as the aging period.

[0008] The ventilation volume during the adaptation period is 2000-2500 L / h, during the growth period it is 3000-3200 L / h, during the stationary period it is 2200-2500 L / h, and during the senescence period it is 1900-2100 L / h.

[0009] By adopting the above technical solution, the fermentation broth for producing avermectin is generally a non-Newtonian fluid, which meets the shear-thinning characteristics. According to the growth characteristics of avermectin production by Streptomyces avermectin, the fermentation process is divided into different stages. The aeration rate is adjusted according to the growth characteristics of different stages, so that the strain can carry out secondary metabolism as early and continuously as possible to achieve better results and increase the yield of avermectin.

[0010] During the adaptation period, the strain grows slowly, and the aeration rate is relatively low, allowing the strain to adapt to the growth environment of the culture medium. In the growth phase, rapid growth causes a rapid increase in the apparent viscosity of the fermentation broth, and the rapid increase in cell mass leads to a rapid increase in oxygen consumption. This increase in apparent viscosity, in turn, reduces the oxygen supply capacity of the fermentation broth. At this point, increasing the aeration rate provides sufficient dissolved oxygen to ensure rapid mycelial growth. In the stationary phase, the cell morphology changes, and the cells begin to form spheres. Oxygen transfer within the spheres is restricted, respiration is limited, the oxygen consumption rate stops increasing, and the apparent viscosity of the fermentation broth gradually decreases. Therefore, it is not necessary to continue increasing the aeration rate; instead, appropriately reducing the aeration rate reduces the dissolved oxygen content in the fermentation broth, preventing excessive dissolved oxygen concentration from affecting the respiration of the spheres. In the aging phase, the growth of the spheres is essentially complete. Reducing the aeration rate, thereby lowering the dissolved oxygen concentration in the fermentation broth, slows down mycelial autolysis, extends the abamectin production time as much as possible, and further increases abamectin yield.

[0011] By adjusting the aeration rate according to the different growth characteristics of the microbial strains during fermentation, the dissolved oxygen concentration in the fermentation broth can be controlled, providing a more favorable environment for the growth of the strains at each stage, which is beneficial to increasing the yield of abamectin. In addition, adjusting the aeration rate according to the growth stage can also reduce gas waste. Taking a 240 kW motor supplying 70 cubic meters of gas per hour as an example, compared to controlling the aeration rate at 2800-3000 L / h throughout the entire growth cycle, approximately 15% of the gas can be saved, reducing gas waste and improving economic efficiency.

[0012] Preferably, the stirring speed is 0 during the adaptation period, 125-135 r / min during the growth period, 80-105 r / min during the stabilization period, and 0 during the aging period.

[0013] By employing the above technical solutions, stirring provides shear force to the fermentation broth, improving its mixing effect and ensuring mass and heat transfer, which is beneficial for increasing abamectin yield. During the adaptation and aging phases, the apparent viscosity of the fermentation broth is low, and aeration itself has a certain mixing and transfer effect. At this time, not stirring will not affect energy transfer in the fermentation broth. Furthermore, the absence of stirring can prevent damage to the strain during the adaptation phase and reduce autolysis of mycelial pellets during the aging phase, which is beneficial for increasing abamectin yield. During the growth and stationary phases, the surface viscosity of the fermentation broth is relatively high. Stirring can mix the fermentation broth, facilitate energy transfer, and ensure mycelial growth.

[0014] In addition, the stirring speed is controlled according to the different growth characteristics of the strains during fermentation. Compared with running at a stirring speed of 130r / min throughout the entire growth cycle, the motor of the mixer is calculated to be 130 kilowatts, which can save about 40% of electricity consumption, reduce resource waste, and improve economic efficiency.

[0015] Preferably, the temperature during the adaptation period is 27-28℃, the temperature during the growth period is 29-30℃, the temperature during the stabilization period is 26-27℃, and the temperature during the senescence period is 25-26℃.

[0016] By adopting the above technical solution, the ambient temperature is controlled according to the different growth characteristics of the strains during fermentation, providing a more favorable environment for the growth of the strains at each stage, which is conducive to increasing the yield of abamectin. Calculated using water heating, compared with operating at a temperature of 27-28℃ throughout the entire growth cycle, the segmented heating method of this application can save approximately 20% of water consumption, reduce water waste, and improve economic efficiency.

[0017] Preferably, at the later stage of the stabilization period, i.e., 200-250 hours, a portion of the fermentation broth is released and replaced with the same volume of fermentation broth that has been cultured for 40-60 hours.

[0018] Preferably, the released fermentation broth accounts for 2-3% of the total volume of the fermentation broth.

[0019] The avermectin fermentation broth generally exhibits non-Newtonian fluid properties. During the fermentation process of *Streptomyces avermectin*, the mycelial morphology changes, the non-Newtonian fluid properties of the fermentation broth gradually weaken, the broth thins, foam gradually increases, and the broth level rises, sometimes resulting in "liquid escape." By adopting the above-mentioned technical solution, a portion of the fermentation broth is released in the later stage of the stationary phase, and new fermentation broth is added. The microorganisms in the added fermentation broth have already entered the growth stage, and the mycelia in the added broth have secondary metabolic capabilities, enabling them to immediately biosynthesize avermectin. In addition, besides reducing the inhibition of metabolic products and maintaining cell vitality, the added fermentation broth contains higher levels of nutrients such as carbon, nitrogen, and nitrogen sources compared to the fermentation broth in the later stage of the stationary phase, providing more energy support for the later biosynthesis of avermectin, which is conducive to the continuous and rapid increase in potency and improves avermectin yield.

[0020] Preferably, the culture medium comprises the following raw materials in parts by weight: 120-140 parts starch, 15-18 parts soybean meal, 3-5 parts yeast powder, 0.1-0.3 parts ammonium sulfate, 0.01-0.03 parts cobalt chloride, 0.01-0.03 parts sodium molybdate, 1-3 parts sodium lactate, 2-4 parts polyethylene glycol, and 8-12 parts sawdust.

[0021] By adopting the above technical solution, starch is used as the carbon source and soybean cake as the nitrogen source in the culture medium to provide basic nutrition for the growth of the strain. In combination with other nutrients, the sodium lactate can be directly converted into propionyl-CoA and methylmalonyl-CoA as secondary metabolic precursors and enter the avermectin molecule. This results in more pyruvate and lactic acid being converted into acetyl-CoA during the fermentation process of the strain. Acetyl-CoA is the most direct precursor for the synthesis of avermectin, which is beneficial to increasing the yield of avermectin.

[0022] Preferably, the polyethylene glycol has a molecular weight of 6000.

[0023] Preferably, the method for preparing the culture medium is as follows:

[0024] 1) Dissolve sodium lactate and polyethylene glycol in water, then add sawdust for absorption, and then dry to obtain mixture A;

[0025] 2) Mix mixture A with the remaining raw materials to obtain the culture medium.

[0026] By adopting the above technical solution, sodium lactate, polyethylene glycol, and sawdust are first mixed. The sawdust adsorbs sodium lactate and polyethylene glycol, which can slowly release sodium lactate, so that the sodium lactate can maintain a stable concentration in the fermentation broth. This avoids the situation where the concentration is too high, the acidity increases, the growth of the cells is inhibited, and the synthesis in the cells is also inhibited, which would lead to a sharp drop in the yield of avermectin. This is conducive to improving the yield of avermectin.

[0027] Secondly, this application provides an abamectin obtained by any of the above-mentioned abamectin fermentation production processes.

[0028] In summary, this application has the following beneficial effects:

[0029] 1. Because this application adjusts the aeration rate in the fermentation broth and controls the dissolved oxygen level in the fermentation broth according to the characteristics of different growth stages of the strain, the strain can carry out secondary metabolism as early and continuously as possible to achieve better results. The abamectin yield can reach 6.89-7.11 g / L, which effectively increases the abamectin yield. Moreover, the flexible adjustment of the aeration rate can effectively reduce gas waste, save resources, and improve overall economic benefits.

[0030] 2. In this application, it is preferred to release part of the fermentation broth and replenish it with the same volume of new fermentation broth in the later stage of the stabilization period. The strains in the replenished fermentation broth have already entered the growth stage. The mycelium in the replenished fermentation broth itself has secondary metabolic capacity and can immediately carry out the biosynthesis of avermectin. In addition to reducing the inhibition of metabolites and maintaining the vitality of the cells, the replenished fermentation broth also provides nutrients, providing more energy support for the biosynthesis of avermectin in the later stage, which is conducive to the continuous and rapid improvement of potency and the increase of avermectin yield. Detailed Implementation

[0031] The present application will be further described in detail below with reference to the embodiments.

[0032] Preparation examples of raw materials and intermediates

[0033] raw material

[0034] All raw materials used in the embodiments of this application are commercially available.

[0035] Ammonium sulfate, cobalt chloride, sodium molybdate, sodium lactate, and polyethylene glycol-6000 are all chemically pure.

[0036] Wood chips, with a fineness of 100-160 mesh.

[0037] Preparation Example

[0038] Preparation Examples 1-5

[0039] 1) According to the raw material ratio in Table 1, dissolve sodium lactate and polyethylene glycol in water, then add sawdust to absorb for 30 minutes, and then dry at 55°C to obtain mixture A;

[0040] 2) Mix mixture A with the remaining raw materials to obtain the culture medium.

[0041] Table 1. Raw material ratios for preparation examples 1-5 (100g)

[0042]

[0043]

[0044] Preparation Example 6

[0045] Preparation Example 6 uses the same raw material ratio as Preparation Example 1, and the preparation method is as follows:

[0046] According to the raw material ratio in Table 1, mix the raw materials other than water to obtain the culture medium.

[0047] Example

[0048] Example 1

[0049] An avermectin, the fermentation production process of which is as follows:

[0050] Abamectin was obtained by inoculating *Streptomyces avermitilis* at a 5% inoculum in the culture medium obtained in Preparation Example 1 and fermenting it. The fermentation conditions were as follows:

[0051] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 27℃, stirring speed of 0;

[0052] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 29℃, stirring speed of 130 r / min;

[0053] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0054] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 25℃, stirring speed of 0.

[0055] Example 2

[0056] Unlike Example 1, the fermentation conditions in Example 2 are as follows:

[0057] Adaptation period 0-20 hours: aeration rate of 2500 L / h, reaction temperature of 27℃, stirring speed of 0;

[0058] Growth period 21-80 hours: aeration rate 3200L / h, reaction temperature 29℃, stirring speed 130r / min;

[0059] Stabilization period 81-250 hours: aeration rate of 2500 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0060] Aging period 251-300 hours: aeration rate of 2100 L / h, reaction temperature of 25℃, stirring speed of 0.

[0061] Example 3

[0062] Unlike Example 1, the fermentation conditions in Example 3 were as follows:

[0063] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 28℃, stirring speed of 0;

[0064] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 28℃, stirring speed of 130 r / min;

[0065] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 28℃, stirring speed of 90 r / min;

[0066] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 28℃, stirring speed of 0.

[0067] Example 4

[0068] Unlike Example 1, the fermentation conditions in Example 4 were as follows:

[0069] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 28℃, stirring speed of 130 r / min;

[0070] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 30℃, stirring speed of 130 r / min;

[0071] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 27℃, stirring speed of 130 r / min;

[0072] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 26℃, and stirring speed of 130 r / min.

[0073] Example 5

[0074] Unlike Example 1, in Example 5, when the reaction had proceeded for 200 hours, 2% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 50 hours.

[0075] Example 6

[0076] Unlike Example 1, in Example 6, when the reaction had proceeded for 250 hours, 2% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 50 hours.

[0077] Example 7

[0078] Unlike Example 1, in Example 7, when the reaction had proceeded for 275 hours, 3% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 50 hours.

[0079] Example 8

[0080] Unlike Example 1, in Example 8, when the reaction had proceeded for 200 hours, 2% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 60 hours.

[0081] Example 9

[0082] Unlike Example 1, in Example 9, when the reaction had proceeded for 200 hours, 2% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 30 hours.

[0083] Example 10

[0084] Unlike Example 1, in Example 10, when the reaction had proceeded for 200 hours, 2% of the total fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 80 hours.

[0085] Examples 11-15

[0086] Unlike Example 5, the culture media in Examples 11-15 were derived from Preparation Examples 2-6, respectively.

[0087] Comparative Example

[0088] Comparative Example 1

[0089] Unlike Example 1, the fermentation conditions in Comparative Example 1 were as follows:

[0090] Adaptation period 0-20 hours: aeration rate of 2800 L / h, reaction temperature of 27℃, stirring speed of 0;

[0091] Growth period 21-80 hours: aeration rate 2800 L / h, reaction temperature 29℃, stirring speed 130 r / min;

[0092] Stabilization period 81-250 hours: aeration rate of 2800 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0093] Aging period 251-300 hours: aeration rate of 2800 L / h, reaction temperature of 25℃, stirring speed of 0.

[0094] Comparative Example 2

[0095] Unlike Example 1, the fermentation conditions in Comparative Example 2 were as follows:

[0096] Adaptation period 0-20 hours: aeration rate of 2800 L / h, reaction temperature of 27℃, stirring speed of 0;

[0097] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 29℃, stirring speed of 130 r / min;

[0098] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0099] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 25℃, stirring speed of 0.

[0100] Comparative Example 3

[0101] Unlike Example 1, the fermentation conditions in Comparative Example 3 were as follows:

[0102] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 27℃, stirring speed of 0;

[0103] Growth period 21-80 hours: aeration rate of 2500 L / h, reaction temperature of 29℃, stirring speed of 130 r / min;

[0104] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0105] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 25℃, stirring speed of 0.

[0106] Comparative Example 4

[0107] Unlike Example 1, the fermentation conditions in Comparative Example 4 were as follows:

[0108] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 27℃, stirring speed of 0;

[0109] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 29℃, stirring speed of 130 r / min;

[0110] Stabilization period 81-250 hours: aeration rate of 2800 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0111] Aging period 251-300 hours: aeration rate of 1900 L / h, reaction temperature of 25℃, stirring speed of 0.

[0112] Comparative Example 5

[0113] Unlike Example 1, the fermentation conditions in Comparative Example 5 were as follows:

[0114] Adaptation period 0-20 hours: aeration rate of 2000 L / h, reaction temperature of 27℃, stirring speed of 0;

[0115] Growth period 21-80 hours: aeration rate of 3000 L / h, reaction temperature of 29℃, stirring speed of 130 r / min;

[0116] Stabilization period 81-250 hours: aeration rate of 2200 L / h, reaction temperature of 26℃, stirring speed of 90 r / min;

[0117] Aging period 251-300 hours: aeration rate of 2500 L / h, reaction temperature of 25℃, stirring speed of 0.

[0118] Performance testing

[0119] Detection methods / test methods

[0120] The abamectin yields in Examples 1-15 and Comparative Examples 1-5 were determined using GC / MS.

[0121] GC conditions were as follows: Agilent HP530m×0.25mm×0.25μm capillary column; injection port temperature: 280℃; temperature program: initial temperature 70℃ held for 2 min, then increased to 290℃ at a rate of 5℃ / min and held for 5 min; carrier gas: high-purity helium, constant pressure mode 91kPa, flow rate 1mL / min; injection volume 1μL; split ratio after column: 10:1.

[0122] MS conditions were as follows: interface temperature: 280℃; ionization mode: EI; ionization mode: electron impact ionization (EI+); ion source temperature: 250℃; electron impact energy: 70eV; electron current: 40μA; scan quality range: 50-800m / z.

[0123] The test results are shown in Table 2.

[0124] Table 2 Performance Test Results

[0125] Avermectin production (g / L) Example 1 6.86 Example 2 6.89 Example 3 6.75 Example 4 6.79 Example 5 7.02 Example 6 6.98 Example 7 6.92 Example 8 7.11 Example 9 6.93 Example 10 6.95 Example 11 7.06 Example 12 7.03 Example 13 6.98 Example 14 6.96 Example 15 6.97 Comparative Example 1 5.28 Comparative Example 2 5.35 Comparative Example 3 5.19 Comparative Example 4 5.39 Comparative Example 5 5.25

[0126] Based on Examples 1-15 and Comparative Examples 1-5, and in conjunction with Table 2, it can be seen that the yield of abamectin in Examples 1-15 is higher than that in Comparative Examples 1-4, indicating that the abamectin fermentation production process of this application yields a higher yield of abamectin.

[0127] Combining Example 1 and Comparative Examples 1-5, and referring to Table 2, it can be seen that in Comparative Example 1, a uniform aeration rate was used throughout the entire growth cycle. Therefore, the abamectin yield in Comparative Example 1 was significantly lower than that in Example 1. This indicates that adjusting the aeration rate according to the characteristics of different growth cycles of the strain is beneficial to increasing abamectin yield. This may be because adjusting the aeration rate ensures that the strain grows at a more suitable dissolved oxygen concentration during different growth stages, allowing the strain to perform secondary metabolism earlier and continuously for better results, thus increasing abamectin yield. In Comparative Example 2, the aeration rate during the adaptation period exceeded the range specified in this application, resulting in a decrease in abamectin yield. This may be because the dissolved oxygen level required by the strain is low in the early adaptation stage. In Comparative Example 3, the aeration rate during the growth period was lower than the range specified in this application, resulting in a decrease in abamectin yield. This may be because during the growth period, the rapid growth of the strain leads to a rapid increase in the apparent viscosity of the fermentation broth, affecting the aeration rate. The rapid increase in volume leads to a rapid rise in oxygen consumption, while the increase in apparent viscosity of the fermentation broth causes a decrease in its oxygen supply capacity. At this point, increasing the aeration rate provides sufficient dissolved oxygen to ensure rapid mycelial growth and increase abamectin production. In Comparative Example 4, the aeration rate during the stationary phase exceeds the limit specified in this application, resulting in a decrease in abamectin production. This may be because after entering the stationary phase, the cell morphology changes, the cells begin to form spheres, respiration is restricted, and the oxygen consumption rate no longer increases. Appropriately reducing the aeration rate reduces the dissolved oxygen content in the fermentation broth, preventing excessively high dissolved oxygen concentrations from affecting the respiration of the mycelial spheres. In Comparative Example 5, the aeration rate during the aging phase exceeds the limit specified in this application, resulting in a decrease in abamectin production. This may be because the growth of the mycelial spheres is basically complete during the aging phase. Reducing the aeration rate slows down the rate of mycelial autolysis, extending the abamectin production time as much as possible, and further increasing abamectin production.

[0128] Combining Examples 1 and 5-10, and referring to Table 2, it can be seen that in Examples 5-10, when a portion of the fermentation broth was released and the same volume of fermentation broth was added during the later stages of the stabilization period, the abamectin yield in Examples 5-10 was higher than that in Example 1. This may be because the newly added fermentation broth strains had already entered the growth stage, and the mycelia in the added fermentation broth themselves had secondary metabolic capabilities, enabling them to immediately carry out the biosynthesis of abamectin. In addition to reducing the inhibition of metabolites and maintaining the vitality of the cells, the added fermentation broth also supplemented nutrients, providing more energy support for the later biosynthesis of abamectin, which is conducive to the continuous and rapid improvement of potency and increases the yield of abamectin.

[0129] Based on Examples 5-7 and Table 2, it can be seen that the yield of abamectin in Examples 5-6 is higher than that in Example 7. This may be because the fermentation broth was released too late in Example 7, and the biosynthesis of abamectin had basically ended. The new fermentation broth had a low participation rate in the biosynthesis of abamectin.

[0130] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A fermentation process for producing avermectin, comprising inoculating *Streptomyces avermectin* into a culture medium for fermentation, characterized in that, The fermentation process is divided into five stages: 0-20 hours is the adaptation period, 21-80 hours is the growth period, 81-250 hours is the stabilization period, and 251-300 hours is the aging period. The ventilation volume during the adaptation period is 2000-2500 L / h, the ventilation volume during the growth period is 3000-3200 L / h, the ventilation volume during the stationary period is 2200-2500 L / h, and the ventilation volume during the senescence period is 1900-2100 L / h. The culture medium comprises the following raw materials in parts by weight: 120-140 parts starch, 15-18 parts soybean meal, 3-5 parts yeast powder, 0.1-0.3 parts ammonium sulfate, 0.01-0.03 parts cobalt chloride, 0.01-0.03 parts sodium molybdate, 1-3 parts sodium lactate, 2-4 parts polyethylene glycol, and 8-12 parts sawdust. The method for preparing the culture medium is as follows: 1) Dissolve sodium lactate and polyethylene glycol in water, then add sawdust for absorption, and then dry to obtain mixture A; 2) Mix mixture A with the remaining raw materials to obtain the culture medium.

2. The avermectin fermentation production process according to claim 1, characterized in that: The stirring speed is 0 during the adaptation period, 125-135 r / min during the growth period, 80-105 r / min during the stabilization period, and 0 during the senescence period.

3. The avermectin fermentation production process according to claim 1, characterized in that: The temperature during the adaptation period is 27-28℃, the temperature during the growth period is 29-30℃, the temperature during the stabilization period is 26-27℃, and the temperature during the senescence period is 25-26℃.

4. The avermectin fermentation production process according to claim 1, characterized in that: During the later part of the stabilization period, i.e., 200-250 hours, some of the fermentation broth was released and replaced with the same volume of fermentation broth that had been cultured for 40-60 hours.

5. The avermectin fermentation production process according to claim 4, characterized in that: The released fermentation broth accounts for 2%-3% of the total volume of the fermentation broth.

6. The avermectin fermentation production process according to claim 1, characterized in that: The molecular weight of the polyethylene glycol is 6000.

7. An abamectin produced by the fermentation process according to any one of claims 1-6.