Streptomyces noursei and application of streptomyces noursei in preparation of multimycotin B

Abstract

The invention relates to the technical field of microorganisms, in particular to streptomyces noursei and application of the streptomyces noursei in preparation of polymycotin B. The invention provides streptomyces noursei GBC A-20 which is preserved in the general microbiological center of the China Committee for Culture Collection of Microorganisms, and the preservation number of the streptomyces noursei GBC A-20 is CGMCC No.27277. The strain can be used for efficiently fermenting and producing the multi-fungal element B by utilizing cheap raw materials, the yield of the multi-fungal element B is remarkably improved, and the chemical titer and the biological titer of the fermentation product nysfungin are greatly improved; the strain and the application thereof provide an economical and feasible solution for the industrial production of the multi-fungal element B and the nysfungin.

Description

Technical Field

[0001] The present invention relates to the field of microbial technology, in particular to Streptomyces noursei and application thereof in preparing polymycin B. Background Art

[0002] Polyfungin B belongs to the class of polyrare macrolide antibiotics. It is a secondary metabolite produced by Streptomyces and is also one of the active ingredients of the antifungal antibiotic nystatin. Nystatin has a broad-spectrum antifungal effect and is mainly used to treat fungal infections of the digestive tract and skin. It has also been reported in agricultural disease control. Although nystatin has been produced and clinically used for many years, there are few reports on the activity and function of its components, and the existing nystatin production technology is still insufficient in terms of economic benefits and active ingredient yield. Studies have shown that nystatin belongs to a multi-component antibiotic, in which the antibacterial potency of each component is the biological potency of polyfungin B> the biological potency of nystatin A1> the biological potency of nystatin A3. Therefore, increasing the content of polyfungin B in nystatin is of great significance for improving the antibacterial activity of nystatin. In addition, there is currently a lack of efficient production strains for the production of polyfungin B. Summary of the invention

[0003] The invention provides a Streptomyces noursei and application of the Streptomyces noursei in preparing polymycin B.

[0004] Specifically, the present invention provides the following technical solutions: The present invention provides Streptomyces noursei ( Streptomyces noursei ) GBC A-20, which was deposited on May 6, 2023 at the General Microbiology Center of China Microorganism Culture Collection Administration (CGMCC, address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing, Institute of Microbiology, Chinese Academy of Sciences, Postal Code 100101), and was classified and named Streptomyces noursei Streptomyces noursei , the deposit number is CGMCC No.27277.

[0005] Based on the research on the main active ingredients of nystatin, the present invention aims to improve the antibacterial activity of nystatin and the content of the main active ingredient polymycin B, and to develop a strain with high yield of polymycin B. Streptomyces noursei ) GBC A-20 is obtained by mutagenesis and screening in the present invention. Experimental verification shows that the chemical potency and biological potency of nystatin produced by it are greatly improved compared with those before mutagenesis. Analysis shows that the proportion of polymycin B in the nystatin produced by it is significantly increased, and the yield of polymycin B in the fermentation broth is significantly increased. This strain is of great significance for increasing the yield of polymycin B, the main active ingredient of nystatin.

[0006] The present invention provides a microbial preparation, wherein the microbial preparation comprises the above-mentioned Streptomyces noursei ( Streptomyces noursei ) GBC A-20.

[0007] Preferably, in the microbial preparation, Streptomyces noursei ( Streptomyces noursei )GBC A-20 exists in the form of live bacteria.

[0008] The microbial preparation may be a liquid preparation or a solid preparation.

[0009] Except for Streptomyces noursei ( Streptomyces noursei ) In addition to GBC A-20, the microbial preparation may also contain excipients permitted in the field of microbial preparations, including but not limited to carriers, lyophilization protectants, etc.

[0010] The above-mentioned microbial preparation can be prepared by conventional technical means, with or without adding auxiliary materials permitted in the field of microbial preparation.

[0011] The present invention also provides a method for preparing the above-mentioned microbial preparation, the method comprising: culturing Streptomyces noursei ( Streptomyces noursei The culturing is preferably carried out at 28-30°C.

[0012] Based on Streptomyces noursei ( Streptomyces noursei ) The function of GBC A-20, the present invention provides the following applications of the strain: The present invention provides the above-mentioned Streptomyces noursei ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation in the preparation of polymycin B.

[0013] The present invention provides the above-mentioned Streptomyces noursei ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation in the preparation of nystatin.

[0014] Preferably, the above application is by culturing the Streptomyces noursei ( Streptomyces noursei ) GBC A-20 obtains polymycin B or nystatin.

[0015] The culture conditions are preferably 28-30°C, pH 6.5-7.0; more preferably pH 6.5.

[0016] The present invention provides the above-mentioned Streptomyces noursei ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation in the preparation of antibacterial or antimicrobial products.

[0017] Preferably, the bacteria are fungi, including but not limited to yeast and the like.

[0018] In the present invention, the product includes medicine, agricultural antimicrobial agent, feed or feed additive.

[0019] The present invention provides the above-mentioned Streptomyces noursei ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation in breeding polymycin B or nystatin production strains.

[0020] The above application is to use Streptomyces noursei ( Streptomyces noursei ) GBC A-20 is bred by breeding methods such as mutagenesis and genetic modification to select the production strain.

[0021] The present invention provides a product comprising Streptomyces noursei ( Streptomyces noursei ) GBC A-20, or containing Streptomyces noursei ( Streptomyces noursei ) A culture or culture broth of GBC A-20, or a purified product containing the culture or culture broth thereof.

[0022] The present invention provides a method for preparing polymycin B or nystatin, the method comprising: treating the above-mentioned Streptomyces noursei ( Streptomyces noursei ) GBC A-20 was used for fermentation culture, and polymycin B or nystatin in the culture was collected.

[0023] Preferably, the culture medium used in the fermentation culture comprises the following components: 44-55 g / L glucose, 15-25 g / L peanut meal, 1-3 g / L silkworm pupa meal, 2-4 g / L peptone, 1-2 g / L soybean oil, 5-15 g / L calcium carbonate, 2-4 g / L ammonium sulfate, 0.01-0.05 g / L potassium dihydrogen phosphate, and 0.3-0.6 g / L magnesium sulfate heptahydrate.

[0024] Preferably, the pH of the fermentation medium is 6.5-7.0.

[0025] Preferably, the fermentation culture conditions are: temperature 28-30°C, pH 6.5-7.0.

[0026] Preferably, the inoculation amount of the fermentation culture is 8%-12%.

[0027] In some specific embodiments of the present invention, the method for preparing polymycin B or nystatin comprises the following steps: (1) Activation of bacterial strains: Streptomyces noursei ( Streptomyces noursei ) GBC A-20 was inoculated on the activation medium and cultured at 28-30°C for 5-7 days until the spores were full; (2) Seed culture: Use an inoculation loop to scrape the mycelium obtained in step (1) above and inoculate it into a seed culture medium. Cultivate it with shaking at 28-30°C and 180-220 rpm for 20-26 h to obtain a seed solution suitable for fermentation. (3) Fermentation culture: The seed solution obtained in step (2) is inoculated into a fermentation medium at an inoculum rate of 8%-12%, and cultured at 28-30°C.

[0028] Preferably, in the above step (1), the activation culture medium comprises the following components: 10.0-25.0 g / L soluble starch, 0.3-0.6 g / L dipotassium hydrogen phosphate, 0.01-0.02 g / L ferrous sulfate heptahydrate, 0.4-0.6 g / L sodium chloride, 0.4-0.6 g / L magnesium sulfate heptahydrate, 0.5-1.5 g / L potassium nitrate, 10.0-20.0 g / L agar, and natural pH.

[0029] Preferably, in the above step (2), the seed culture medium comprises the following components: 5-15 g / L starch, 5-7 g / L calcium carbonate, 5-15 g / L glucose, 1-3 g / L ammonium sulfate, 15-25 g / L peanut meal, 0.1-0.3 g / L potassium dihydrogen phosphate, 1-3 g / L peptone, 2-4 g / L soybean oil, 0.4-0.6 g / L magnesium sulfate heptahydrate, and pH 6.8-7.4.

[0030] The beneficial effects of the present invention are as follows: the present invention obtains the high-yield polymycin B Streptomyces noursei CGMCC No.27277 through sodium nitrite mutagenesis breeding screening, the strain can use cheap raw materials to efficiently ferment and produce polymycin B, and the yield of polymycin B is significantly improved; the content of polymycin B in the prepared nystatin is significantly improved, the chemical potency is 21538 U / mL after 72 hours of shake flask fermentation, the biological potency is 8412 U / mL, and the fungal inhibitory activity is significantly improved; the strain and the application thereof provide an economically feasible solution for the industrial production of polymycin B and nystatin. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 This is the sodium nitrite-induced lethality curve in Example 1 of the present invention.

[0033] Figure 2The HPLC test results of the standard in Example 3 of the present invention are as follows, wherein a: nystatin standard, b: nystatin standard; the component of the nystatin standard is nystatin A1, which is used to determine its retention time under the chromatographic conditions; the nystatin standard is a multi-component product, including nystatin A1, nystatin A3 and polymycin B, which is used to locate the components under the chromatographic conditions; the abscissas in a and b are 0, 5, 10, 15, 20, 25 min from left to right, and the ordinate unit is mAu.

[0034] Figure 3 These are the HPLC test results of the refined fermentation product of Streptomyces noursei CGMCC No.27277 in Example 3 of the present invention, wherein a: nystatin standard; b: refined fermentation product of the starting strain (i.e., 72-22-1); and c: refined fermentation product of Streptomyces noursei CGMCC No.27277.

[0035] Figure 4 The biological potency test results of Streptomyces noursei CGMCC No.27277 in Example 4 of the present invention are shown, wherein SH: high concentration of nystatin standard (80U / mL); SL: low concentration of nystatin standard (40U / mL); UH: high concentration of sample (80U / mL); UL: low concentration of sample (40U / mL); the left figure is the starting strain (marked as 72-22-1 in the figure), and the right figure is strain CGMCC No.27277 (marked as C-21 in the figure). DETAILED DESCRIPTION

[0036] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the drawings of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples are all commercially available unless otherwise specified.

[0038] Example 1 Mutation breeding and screening of polymycin B producing strains The present invention is based on Streptomyces noursei ( Streptomyces noursei ) was used as the starting strain, and a strain that can efficiently produce polymycin B was successfully screened out through the method of sodium nitrite mutagenesis, and was named Streptomyces noursei ( Streptomyces noursei ) GBC A-20.

[0039] Streptomyces noursei ( Streptomyces noursei GBC A-20 was deposited on May 6, 2023 at the General Microbiology Center of China Microorganism Culture Collection Administration (CGMCC, address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, Institute of Microbiology, Chinese Academy of Sciences, Postal Code 100101), and was named Streptomyces noursei Streptomyces noursei , the deposit number is CGMCC No.27277.

[0040] The specific strain mutagenesis and screening process is as follows: The present invention carries out sodium nitrite mutagenesis on the starting strain for 5 times, and Streptomyces noursei is used as the starting strain for the first sodium nitrite mutagenesis; the following only takes the first sodium nitrite mutagenesis and screening process as an example for description, and each subsequent sodium nitrite mutagenesis uses the high-yield strain of polymycin B obtained in the previous screening as the starting strain, and repeats the following mutagenesis screening process.

[0041] 1. Sodium nitrite mutagenesis (1) Preparation of single spore suspension: The starting strain was inoculated onto Gao's synthetic medium No. 1 (formula is as follows: soluble starch 20.0 g / L, magnesium sulfate heptahydrate 0.5 g / L, potassium dihydrogen phosphate 0.5 g / L, potassium nitrate 1.0 g / L, ferrous sulfate heptahydrate 0.01 g / L, sodium chloride 0.5 g / L, agar 14.0 g / L, natural pH, prepared with distilled water, sterilized at 121°C for 20 min), and cultured at 28°C for 7 days. A certain volume of physiological saline was added under sterile conditions, spores were scraped with an inoculation loop, and a single spore suspension was obtained by shaking and filtering out impurities. The spore suspension was counted by a hemocytometer and adjusted to 10 6 The concentration of CFU / mL is used for future use.

[0042] (2) Sodium nitrite mutagenesis treatment: Take 1 mL of spore suspension in a 50 mL centrifuge tube, add 2 mL of pH 4.5 acetic acid solution and 1 mL of 0.05 M sodium nitrite solution to the centrifuge tube, and the final concentration of sodium nitrite treatment is 0.0125 M. After keeping warm at 25 °C for 0 min, 3 min, 6 min, 9 min, 12 min, and 15 min, add 20 mL of pH 8.6 disodium hydrogen phosphate solution to reduce the pH to about 6.8 to terminate the reaction, and dilute the spore suspension in a gradient manner. Select 10 -2 , 10 -3 , 10 -4 Take 100 μL of the bacterial suspension of each dilution and spread it on a plate of Gao's synthetic medium No. 1. Make three parallel groups for each gradient and culture at 28 ℃ for 5-7 days. Count the number of colonies and calculate the lethality.

[0043] The sodium nitrite mutation lethality curve of Streptomyces noursei is as follows Figure 1 The lethality of Streptomyces noursei spores was 57.47% when treated with sodium nitrite for 3 min, and reached 84.07% at 6 min. Finally, the surviving strains treated with sodium nitrite for 3 min were selected for subsequent screening.

[0044] 2. Preliminary screening of sodium nitrite mutagenesis In the mutagenesis breeding project, keeping the lethality between 70% and 80% can usually obtain more positive mutations. Considering the intensity of the screening work, a single colony on a plate with a lethality of 60% to 80% was selected for amplification and culture for 7 days, then inoculated into the fermentation medium, and cultured at 28°C and 200 r / min for 72 hours. The chemical titer of nystatin in the fermentation product was determined, and the best was rescreened according to the determination results. For the determination method of chemical titer and biological titer, please refer to pages 2888-2889 of the European Pharmacopoeia 8.0.

[0045] The 176 mutant strains obtained by mutagenesis were divided into 8 batches for initial screening, with 22 mutant strains and 2 starting strains cultured in each batch as references.

[0046] 3. Rescreening of mutagenic strains The rescreening focuses on the accuracy and repeatability of the experiment, and strives to obtain reliable experimental results. Therefore, during the rescreening, one strain is usually inoculated into three bottles of fermentation medium, and two-stage fermentation is performed using seed shake flasks and fermentation shake flasks. The mutant strain with a higher chemical titer measured during the initial screening is inoculated into the liquid seed medium for fermentation. After shaking culture at 28 °C and 200 r / min for 24 hours, the seed culture liquid is transferred to the fermentation medium at an inoculation rate of 10%, and cultured under the same conditions as above for 72 hours. The chemical titer of nystatin in the fermentation liquid is determined to screen mutants with excellent nystatin production characteristics.

[0047] The OD of the fermentation extract was measured by UV spectrophotometer. 319 The chemical titer was calculated by the PCR and 11 mutants with a unit nystatin production titer of more than 1.3 times that of the starting strain were screened. Among them, the strain CGMCC No.27277 had the highest unit production, which could reach 21538 U / mL.

[0048] The five mutants with the highest chemical potency in the rescreening, 1-45, 1-54, CGMCC No. 27277, D-12, and H-3, were selected, and their fermentation products were extracted and purified (refer to Example 3 for the purification method), and then the biological potency was measured. The results are shown in Table 1.

[0049] Table 1 Bioavailability test results (mean and standard deviation; n=3)

[0050] The results showed that the biological potency of the refined product of the fermentation broth of Streptomyces noursei CGMCC No. 27277 was the highest, reaching 8412 U / mg, which was 86.8% higher than that of the starting strain and higher than the biological potency of the commercially available nystatin standard (5581 U / mg, the standard was from the China Food and Drug Inspection Institute). The above results also further prove that the biological potency of polymycin B is much higher than that of nystatin A1 and nystatin A3.

[0051] Example 2 Shake flask fermentation experiment for producing polymycin B The fermentation conditions were optimized for the Streptomyces noursei CGMCC No.27277 with the best fermentation performance, and the optimal fermentation medium formula and fermentation conditions were determined.

[0052] A shake flask fermentation experiment of polymycin B production by Streptomyces noursei CGMCC No. 27277 was carried out under the optimal fermentation medium and fermentation conditions to investigate the fermentation performance of the strain Streptomyces noursei CGMCC No. 27277, with the starting strain as the control. The specific method is as follows: (1) Activation of bacterial strains: Inoculate Streptomyces noursei CGMCC No. 27277 and the starting strain on Gao's medium No. 1 activation plates, respectively, and culture at 28°C for 7 days; (2) Seed culture: The activated Streptomyces noursei CGMCC No. 27277 and the starting strain in step (1) were inoculated into liquid seed culture medium respectively, and cultured at 28°C and 150 rpm for 24 h; (3) Fermentation culture: The seed solution obtained in step (2) was inoculated into a fermentation medium at a rate of 10%, and cultured at 28°C, 180 rpm, for 72 h.

[0053] The formula of the liquid seed culture medium is as follows: starch 10.0 g / L, calcium carbonate 6.0 g / L, glucose 10.0 g / L, ammonium sulfate 2.0 g / L, peanut meal 20.0 g / L, potassium dihydrogen phosphate 0.2 g / L, peptone 2.0 g / L, soybean oil 3.0 g / L, magnesium sulfate heptahydrate 0.5 g / L, pH 7.2.

[0054] The formula of the above fermentation medium is as follows: glucose 44.0 g / L, peanut cake powder 15.0 g / L, silkworm pupa powder 2.0 g / L, peptone 3.0 g / L, soybean oil 1.0 g / L, calcium carbonate 10.0 g / L, ammonium sulfate 3.0 g / L, potassium dihydrogen phosphate 0.020 g / L, magnesium sulfate heptahydrate 0.5 g / L, pH 6.5.

[0055] Example 3 HPLC Detection of Polymycin B The content of polymycin B in the fermentation broth obtained in Example 2 was detected by HPLC, and the specific method was as follows: (1) Sample pretreatment (refining) ① Stir the fermentation liquid evenly, draw 5 mL into a centrifuge tube, add 30 mL of distilled water, stir evenly, centrifuge at low speed for 10 minutes, and discard the supernatant; repeat centrifugation to wash the bacteria 3 times; ②Take 20mL of methanol and add it to the above-mentioned mycelium. Stir the mycelium with a glass rod for a while, let it stand overnight, centrifuge, remove the supernatant and set aside.

[0056] (2) HPLC detection Chromatographic column: Elite Hypersil BDSC18 (250×4.6mm, 5μm); Mobile phase: methanol (chromatographic grade): acetate buffer (sodium acetate 7.72 g, add water 200 mL, shake to dissolve, add glacial acetic acid 16 mL, dilute to 2000 mL with water): acetonitrile (chromatographic grade) = 37:37:26; Flow rate: 1 mL / min; injection volume: 10 μL; detection wavelength: 305 nm; column temperature: 30°C.

[0057] The HPLC test results of nystatin standard and nystatin standard are as follows Figure 2 After the fermentation product of Streptomyces noursei CGMCC No.27277 was extracted and purified (i.e., the aforementioned pretreatment), the components were detected and analyzed using HPLC. The results are shown in Figure 3 shown.

[0058] Depend on Figure 3It can be concluded that the retention times of the three components of nystatin A1, nystatin A3 and polymycin B in the refined product of the fermentation product of Streptomyces noursei CGMCC No. 27277 are 12.981 min, 16.441 min and 22.042 min, respectively. Among them, the content of nystatin A3 in the nystatin standard is the highest, which is 59.14%; the content of nystatin A1 in the refined product of the fermentation product of the starting strain is the highest, which is 40.13%, and the content of polymycin B is 32.67%; and the content of polymycin B in the refined product of the fermentation product of Streptomyces noursei CGMCC No. 27277 is the highest, which is 45.29%.

[0059] It can be seen that the yield of polymycin B of Streptomyces noursei CGMCC No. 27277 and its proportion in the fermentation product nystatin are greatly improved compared with the starting strain, and combined with the results in Table 1, it can be seen that its biological efficacy is also greatly improved.

[0060] Example 4 Antifungal Activity Analysis of the Fermentation Broth of Streptomyces noursei CGMCC No. 27277 The two-dose method in the tube-plate method was used to determine the biological potency of the fermentation broth of Streptomyces noursei CGMCC No. 27277, and the antifungal activity of the fermentation broth of Streptomyces noursei CGMCC No. 27277 was analyzed. The specific operation is as follows: 1. Preparation of Saccharomyces cerevisiae 2061 spore suspension Inoculate brewer's yeast into YM slant medium (formula as follows: peptone 5.0 g / L, malt extract 3.0 g / L, glucose 10.0 g / L, agar 20.0 g / L, yeast powder 3.0 g / L, pH 6.2, prepared with distilled water, 115°C, sterilize for 30 min), culture at 28°C for 2-3 days, and store at 4°C.

[0061] When using, add 5 mL of physiological saline to the YM slant medium full of Saccharomyces cerevisiae 2061, scrape off the spores with an inoculation loop, mix and pour into a triangular flask containing glass beads, shake for 20 minutes, pour into a syringe filled with absorbent cotton, filter, and collect the yeast liquid in a sterile clean test tube. Take 0.25 mL in 20 mL of YM medium cooled to about 45°C, mix and culture for 48 hours, titrate the concentration of the bacterial liquid with 80 U / mL nystatin standard to an inhibition zone diameter of 18-24 mm, and store in a refrigerator at 4°C for later use.

[0062] 2. Bioavailability Determination The refined product of the fermentation broth of Streptomyces noursei CGMCC No. 27277 obtained in Example 2, the refined product of the fermentation broth of the starting strain, and the nystatin standard were dissolved in N,N-dimethylformamide to obtain a 1000 U / mL solution; and then diluted with PBS to 80 U / mL (high dose) and 40 U / mL (low dose), respectively.

[0063] Pour 15mL YM medium into a 90 mm plate as the bottom medium, take 0.25mL of the titrated yeast suspension and add it to 20mL of YM medium cooled to about 45℃ and mix well, take 8mL and spread it on the surface of the cooled bottom medium, after cooling, place 4 Oxford cups diagonally, add 200μL of high and low doses of sample and standard respectively, cover with a clay lid, place for half an hour, and culture in a constant temperature incubator at 28℃ for 2 days. The inhibition zone results are as follows: Figure 4 shown.

[0064] In summary, the present invention successfully bred a high-yield polymycin B strain, Streptomyces noursei CGMCC No. 27277, through mutagenesis breeding, and established a stable seed culture and fermentation production process thereof, thereby providing an economically feasible approach for the production and application of polymycin B in medicine and agriculture, improving the controllability and reproducibility of the fermentation process, and also improving the product quality and production efficiency, which plays an important role in promoting the market competitiveness of polymycin B and nystatin.

[0065] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Streptomyces noursei ( Streptomyces noursei ) GBC A-20, characterized in that, It is deposited in the General Microbiology Center of China Microorganism Culture Collection Administration with the deposit number CGMCC No.27277.

2. A microbial preparation, characterized in that: The microbial preparation comprises the Streptomyces noursei described in claim 1 ( Streptomyces noursei ) GBC A-20.

3. The Streptomyces noursei of claim 1 ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation described in claim 2 in the preparation of polymycin B.

4. The Streptomyces noursei of claim 1 ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation described in claim 2 in the preparation of nystatin.

5. The Streptomyces noursei of claim 1 ( Streptomyces noursei ) Use of the microbial preparation described in GBC A-20 or claim 2 in the preparation of antibacterial or antibacterial products.

6. The use according to claim 5, characterized in that: The product is a medicine, an agricultural antibiotic, a feed or a feed additive.

7. The Streptomyces noursei of claim 1 ( Streptomyces noursei ) Use of GBC A-20 or the microbial preparation described in claim 2 in breeding strains for producing polymycin B or nystatin.

8. A method for preparing polymycin B or nystatin, characterized in that: The method comprises: treating the Streptomyces noursei described in claim 1 ( Streptomyces noursei ) GBC A-20 was used for fermentation culture, and polymycin B or nystatin in the culture was collected.

9. The method according to claim 8, characterized in that The culture medium used in the fermentation culture comprises the following components: 44-55 g / L of glucose, 15-25 g / L of peanut cake powder, 1-3 g / L of silkworm pupa powder, 2-4 g / L of peptone, 1-2 g / L of soybean oil, 5-15 g / L of calcium carbonate, 2-4 g / L of ammonium sulfate, 0.01-0.05 g / L of potassium dihydrogen phosphate, and 0.3-0.6 g / L of magnesium sulfate heptahydrate.

10. The method according to claim 8 or 9, characterized in that: The fermentation culture conditions are: temperature 28-30°C, pH 6.5-7.0; And / or, the inoculation amount of the fermentation culture is 8%-12%.

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