Streptomyces globosus, culture medium, fermentation method, biological bacteriostatic agent and application of biological bacteriostatic agent

Abstract

The invention relates to the technical field of microbial fermentation engineering, in particular to streptomyces globosus, a culture medium, a fermentation method, a biological bacteriostatic agent and application of the biological bacteriostatic agent. On the basis of streptomyces globosus ZJU704 (the preservation number is CGMCC (China General Microbiological Culture Collection Center) NO.36895), thallus growth and synthesis of bacteriostatic active substances are remarkably promoted by optimizing culture medium components of the streptomyces globosus ZJU704. The invention further discloses a fermentation method using the streptomyces globosus and the special culture medium, and a high-activity biological bacteriostatic agent can be prepared. The effective component of the biological bacteriostatic agent comprises partricin B, and the biological bacteriostatic agent has a broad-spectrum inhibition effect on various microorganisms such as bacillus subtilis, escherichia coli, saccharomycetes and fusarium graminearum.

Description

Technical Field

[0001] This invention relates to the field of microbial fermentation engineering technology, specifically to a Streptomyces globosum, a culture medium, a fermentation method, a biological antibacterial agent, and their applications. Background Technology

[0002] Streptomyces ( Streptomyces Streptomyces (Streptomyces) is a Gram-positive bacterium belonging to the genus Streptomyces in the family Streptomycetes. During its growth, it readily forms highly branched and resistant hyphae. Upon maturity, the aerial hyphae further develop into characteristic chain-like structures composed of conidia. Most compounds in Streptomyces are obtained through fermentation and extraction of pure fermentation products from the strain. Its metabolites are a significant source of many microbial-derived clinical antibiotics and natural drugs. Currently, fermentation followed by extraction is the primary route for obtaining Streptomyces metabolites. Therefore, developing and optimizing Streptomyces fermentation methods is a prerequisite for deeply exploring and utilizing the potential of its metabolites.

[0003] In the fermentation and development of Streptomyces, the optimization of the culture medium is a core element determining the yield and types of its metabolites. The synthesis of Streptomyces' secondary metabolites, such as antibiotics like streptomycin and tetracycline, as well as antitumor drugs and immunosuppressants, is highly sensitive to environmental nutrients. For example, rapidly utilized carbon sources like glucose typically promote cell growth, while slowly utilized carbon sources like starch are more conducive to the accumulation of antibiotics such as tetracycline. Culture media rich in organic nitrogen sources, such as ISP-2, are often used to promote aerial mycelial formation, and certain specific components affect cell growth and secondary metabolic pathways through different regulatory mechanisms. Therefore, optimizing the culture medium formulation is not only a necessary means to increase the yield of target products but also a key strategy for triggering silent gene clusters and discovering new compounds.

[0004] CN112575023B discloses a method for efficiently expressing phospholipase D in Streptomyces. Two Streptomyces-derived phospholipase D genes were screened and cloned, and constructed into common and high-efficiency expression vectors, respectively. These vectors were then introduced into host Streptomyces. Finally, the optimal recombinant strain for heterologous high-efficiency expression of phospholipase D was screened by comparing fermentation and enzyme activity. CN116814723B discloses a fermentation method for Streptomyces 5406 that simultaneously produces auxin and cytokinin. Streptomyces 5406 is cultured in ordinary Gao's No. 1 medium with the addition of tryptophan and lactose, simultaneously producing cytokinin and auxin.

[0005] Current technologies for the development and utilization of Streptomyces primarily focus on the targeted enhancement of the expression of specific target products. The mainstream approach is to increase the yield of a single or a few known metabolites through technological intervention. This neglects the potential of Streptomyces' overall metabolic profile, particularly its broad-spectrum antibacterial activity. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a Streptomyces globosum, a culture medium, a fermentation method, a biological antibacterial agent, and their applications.

[0007] The technical solution adopted in this invention is as follows: In a first aspect, this invention provides a strain of *Streptomyces circumflexus* ZJU704, classified and named *Streptomyces circumflexus* (… Streptomyces globosus The accession number is CGMCC NO.36895, and it is deposited at the China General Microbiological Culture Collection Center, Institute of Microbiology, Chinese Academy of Sciences, No. 3, Beichen West Road, Chaoyang District, Beijing. The deposit date is December 4, 2025.

[0008] In a second aspect, the present invention provides a fermentation medium for *Streptomyces globosum*, wherein the medium is selected from any of the following: (a) Yeast extract 3~5g / L, starch 5~15g / L, peptone 1~3g / L, mannitol 3~5g / L, sea salt 30~35g / L, pH 7.3~7.5; (b) Glucose 5~15g / L, corn steep liquor 5~15g / L, soybean flour 5~15g / L, glycerol 3~7g / L, dry yeast 3~7g / L, NaCl 3~7g / L, CaCO3 1~3g / L, pH 5.6~5.8; (c) Soluble starch 5~15g / L, glucose 5~15g / L, peptone 6~8g / L, yeast extract 1~3g / L, glycerol 5~15g / L, corn extract 2~3g / L, sea salt 30~35g / L, CaCO3 2~4g / L, pH 6.8~7.2.

[0009] In a third aspect, the present invention provides a method for fermenting *Streptomyces globosum*, wherein the method employs *Streptomyces globosum* ZJU704 as described in claim 1 (… Streptomyces globosus ZJU704), and includes the following steps: (a) Fermenting *Streptomyces flocculationensis* in the culture medium of claim 2; (b) After fermentation, the fermentation broth is separated and purified to obtain a supernatant containing antibacterial activity.

[0010] Further, in step (a), the inoculum size of *Streptomyces globosum* is 10. 5 ~10 7 CFU / mL; Further, in step (a), the fermentation conditions of the white Streptomyces are: 28~32°C, 150~200rpm, and shaking culture under dark conditions for 5~9 days.

[0011] Further, in step (b), the separation and purification includes: adsorbing the fermentation broth onto a macroporous resin, eluting with a gradient of 20% to 100% ethanol by volume, with an elution volume of 1 to 5 column volumes, and collecting the eluent.

[0012] More preferably, the macroporous resin is AB-8 type macroporous resin.

[0013] More preferably, the volume fraction of the ethanol solution is 60%.

[0014] More preferably, the elution volume is 3 column volumes.

[0015] In a fourth aspect, the present invention provides a biological antibacterial agent, which is prepared by the aforementioned method.

[0016] Furthermore, the effective antibacterial component of the bio-antibacterial agent includes partricin B.

[0017] The present invention provides, in a fifth aspect, the use of the aforementioned bio-antimicrobial agent in inhibiting microorganisms selected from at least one of the following: A1) Bacillus subtilis; A2) Escherichia coli; A3) Yeast; A4) Fusarium graminearum; The Bacillus subtilis is preferably Bacillus subtilis 3610; The preferred Escherichia coli is Escherichia coli DH5α; The yeast strain is preferably yeast BY4741; The preferred Fusarium species is Fusarium graminearum PH-1.

[0018] Compared with the prior art, the present invention has the following beneficial effects: (1) This invention screened a variety of fermentation culture media for Streptomyces globosum ZJU704, which can effectively promote the proliferation of bacteria and efficiently synthesize the target antibacterial active substances.

[0019] (2) The main active ingredient of the biological antibacterial agent prepared by the technical solution of the present invention is clearly partricin B. Experiments have confirmed that the antibacterial agent exhibits strong inhibitory activity against Gram-positive bacteria (such as Bacillus subtilis), Gram-negative bacteria (such as Escherichia coli), fungi (such as yeast), and important plant pathogens (such as Fusarium graminearum), showing broad-spectrum and highly efficient antibacterial characteristics. Attached Figure Description

[0020] Figure 1 Streptomyces circinus ( Streptomyces globosus The strain morphology is described, and the strain number is ZJU704.

[0021] Figure 2 This invention presents a phylogenetic tree of Streptomyces circinus ZJU704 constructed based on the whole genome.

[0022] Figure 3 To characterize the inhibition of Bacillus subtilis (B) by each component after gradient elution with macroporous resin using the disc diffusion method. acillis subtilis Experimental results of NCBI 3610 activity.

[0023] Figure 4 To characterize the inhibition of Escherichia coli by each component after gradient elution with macroporous resin using the disc diffusion method (CDF), Escherichia coli Experimental results of DH5α activity.

[0024] Figure 5 To characterize the inhibition of yeast by each component after gradient elution with macroporous resin using the disc diffusion method. Aaccharomyces cerevisiae Experimental results of the activity of BY4741.

[0025] Figure 6 To characterize the inhibition of *Streptococcus graminearum* by each component after gradient elution with macroporous resin using the disc diffusion method (CDF), Fusarium graminearum Experimental results of PH-1 activity.

[0026] Figure 7 This is the structure of partricin B.

[0027] Figure 8 The base peak chromatogram and partricin B primary and secondary mass spectra of the fraction eluted with 60-80% ethanol were obtained by liquid chromatography-mass spectrometry. Detailed Implementation

[0028] To enable those skilled in the art to better understand the technical content of the present invention, the present invention will be further described below in conjunction with specific embodiments and accompanying drawings.

[0029] Test culture medium: Tryptic Soy Agar (TSA): Tryptic peptone 15.0 g / L, Soy peptone 5.0 g / L, Sodium chloride 5.0 g / L, Agar 15.0 g / L, pH 7.1~7.5; R2A medium (Reasoner's 2A Agar): Casein trypsin digest 0.5 g / L, yeast extract 0.5 g / L, peptone 0.5 g / L, glucose 0.5 g / L, soluble starch 0.5 g / L, dipotassium hydrogen phosphate 0.3 g / L, anhydrous magnesium sulfate 0.05 g / L, sodium pyruvate 0.3 g / L, agar 15.0 g / L, pH 7.0~7.4; WA medium (Water Agar): 1000 mL distilled water, 15.0-20.0 g / L agar, pH 6.6-7.0; ISP2 medium (International Streptomyces Project medium 2): yeast extract 4.0 g / L, malt extract 10.0 g / L, glucose 4.0 g / L, agar 20.0 g / L, pH 7.2-7.4; MH medium (Mueller-Hinton Agar / Broth, MHA / MHB): acid-hydrolyzed casein 17.5 g / L, beef extract powder (or extract powder) 2.0-6.0 g / L, soluble starch 1.5 g / L, agar 13.0-17.0 g / L, pH 7.2-7.4; YPDA medium (Yeast Extract Peptone Dextrose Adenine Medium): Yeast extract 10g / L, Peptone 20g / L, Dextrose 20g / L, Adenine 0.02%, Agar 20-24g / L; PDA medium (Potato Dextrose Agar): 200 g / L potato (peeled and diced) (boiled and filtered to obtain juice, by juice volume), 20.0 g / L glucose, 15.0-20.0 g / L agar, pH 5.0-6.0.

[0030] Unless otherwise specified, the experimental methods used in this invention are all conventional experimental methods in the field; the materials, reagents and instruments used are all conventional materials, reagents and instruments in the field, which can be obtained through commercial channels or prepared by conventional methods.

[0031] Example 1: Identification of strain ZJU704 (1) Preparation of strains Wheat rhizosphere soil samples from different collection sites were placed in 50 mL sterile centrifuge tubes, and 20 mL of sterile water was added to prepare a suspension. The suspension was then shaken at 180 rpm for 30 min in a shaker to ensure thorough dispersion of microorganisms. An appropriate amount of the suspension was then transferred to a 2 mL sterile EP tube and subjected to 10 cycles of centrifugation. -1 10 -2 10 -3Dilute with concentration gradients; 100 μL of each dilution was taken and spread sequentially onto TSA, 10% TSA, and R2A agar plates containing 5 μg / mL carbendazim for bacterial isolation using a sterile spreader; the inoculated plates were placed in a 30°C incubator for 7 days, during which colony growth was observed regularly; single colonies with different morphological characteristics (including size, color, etc.) were picked and transferred to WA and ISP2 plates for purification culture; finally, the purified strains were stored in 30% glycerol at -80°C for long-term preservation, and systematically classified and numbered according to the sample collection location.

[0032] (2) Strain identification Whole-genome sequencing was performed on the bacterial strains to assess the genomic DNA quality. Acceptable DNA samples were randomly fragmented to approximately 350 bp using a Covaris fragmenter. The fragmented DNA underwent end repair, 5' phosphorylation, and 3' A-tailing. Illumina sequencing adapters were then ligated to both ends of the DNA fragments. The ligation products were screened using a two-step (Double Size Selection) method with SPRI magnetic beads. The selected libraries were enriched by high-fidelity PCR amplification. The concentration of the amplified products was determined using Qubit 3.0, the insert size was detected using an Agilent 5400 system, and the effective library concentration (target 1.5 nM) was accurately quantified using qPCR. Quality-tested libraries were sequenced on the Illumina Novaseq platform. The libraries were first amplified into DNA clusters using Bridge PCR on FlowCell, followed by PE150 (Pair-end 150 bp) paired-end sequencing to obtain raw data in FASTQ format. The raw data was quality controlled using the FastP software, with the following filtering rules: 1) Remove read pairs containing adapters; 2) Read pairs with a nitrogen base ratio of 10% or higher were removed; 3) Remove low-quality read pairs (defined as reads in which the number of bases with Q≤5 accounts for more than 50% of any given read).

[0033] The obtained clean data was used for subsequent genome assembly and bioinformatics analysis. Gene analysis was performed using sequencing data, and assembly was performed using SPAdes v4.1.0. The "streptomycetales_odb10" database in BUSCO v5.2.2 was used to identify conserved genes, thus assessing the quality of genome assembly. Genome annotation used the "light" database in bakta v1.9.4. The "streptomycetales_odb10" database in BUSCO v5.2.2 (-m prot) was used to identify conserved genes, thus assessing the quality of genome annotation.

[0034] Phylogenetic analysis was performed using genomes of 20 publicly available Streptomycetales species from the NCBI database, and their genome quality was assessed using BUSCO v5.2.2 software. A phylogenetic tree was constructed using 198 single-copy BUSCO genes, which are present in at least half of all Streptomycetales species. Each BUSCO gene was aligned using MAFFT v7.525 with the "--auto" option, and ambiguous alignment regions were removed using the "gappyout" function of trimAl v1.5. PhyKIT v2.0.1 software was then used to integrate the nucleotide sequence alignment results of these 198 BUSCO genes into a complete data matrix. Finally, IQ-TREE version 2.4.0 was used, and the optimal TVM+F+R10 model was found using -m MFP for maximum likelihood phylogenetic analysis. Figure 1 The strain ZJU704 was ultimately identified as *Streptomyces globosum*. Streptomyces globosus The sample is deposited at the China General Microbiological Culture Collection Center (CGMCC), Institute of Microbiology, Chinese Academy of Sciences, No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, with accession number CGMCC NO. 36895 and deposit date of December 4, 2025. Figure 2 ).

[0035] Example 2: Screening and Fermentation Methods for Culture Media To screen for the optimal fermentation medium, the following ten representative media were prepared for comparison: Culture medium ①: tryptone 20 g / L, lactose 15 g / L, salicin 0.8 g / L, NaCl 5 g / L, Triton X-100 2.0 g / L; pH 7.0; Culture medium ②: yeast extract 4.0 g / L, starch 10.0 g / L, peptone 2.0 g / L, mannitol 4.0 g / L, sea salt 33.5 g / L, pH 7.4; Culture medium ③: millet 20.0 g / L, glucose 20.0 g / L, peptone 3.0 g / L, CaCO3 2.0 g / L, NaCl 2.5 g / L; Culture medium ④: glucose 10g / L, corn steep liquor 10g / L, soybean flour 10g / L, glycerol 5g / L, dry yeast 5g / L, NaCl 5g / L, CaCO3 2g / L, pH 5.7; Culture medium ⑤: soluble starch 10g / L, glucose 10g / L, peptone 7g / L, yeast extract 2g / L, glycerol 10g / L, corn extract 2.5g / L, sea salt 33.5g / L, CaCO3 3g / L, pH 7.0; Culture medium ⑥: glucose 10g / L, tryptophan 2g / L, yeast extract 1g / L, beef extract 1g / L, glycerol 5g / L, NaCl 32g / L, distilled water 1 L; Culture medium ⑦: soluble starch 35g / L, NH4NO3 3.5g / L, K2HPO4 1g / L, MgSO4·7H2O 0.5g / L, CaCO3 3g / L, pH 7.0; Culture medium ⑧: sucrose 40 g / L, corn flour 20 g / L, corn steep liquor 20 g / L, (NH)₂SO₄ 2 g / L, KH₂PO₄ 1 g / L, MgSO₄ 1 g / L, MnSO₄·H₂O 0.01 g / L, ZnSO₄·7H₂O 0.01 g / L, pH 7.2~7.4; Culture medium ⑨: glucose 20g / L, maltose 15g / L, peptone 2g / L, yeast extract 1g / L, NaNO3 4g / L, K2HPO4·3H2O 1g / L, MgSO4·7H2O 1g / L, FeSO4·7H2O 0.02g / L, CaCO3 3g / L; Culture medium ⑩: Maltose extract 10 g / L, glucose 10 g / L, corn flour 5 g / L, soluble starch 20 g / L, maltose 10 g / L, trace elements 100 μL, pH 7.2-7.5. (Trace elements: ZnCl2 0.8 g / L, FeCl3·6H2O 4 g / L, CuCl2·2H2O 0.2 g / L, MnCl2·4H2O 0.2 g / L, NaB4O7·10H2O 0.2 g / L).

[0036] Fermentation method: The above-mentioned Streptomyces flocculation strain was fermented at 10... 6Inoculation at CFU / mL was performed into 10 different culture media with varying ratios, and fermentation was carried out at 30°C, 180 rpm, and in the dark for 7 days with shaking. After fermentation, the fermentation broth was centrifuged at 5000 rpm for 10 minutes, and the supernatant was collected. The supernatant was then filtered through a 0.22µm microporous membrane for sterilization. The resulting supernatant was the composition with primary antibacterial activity and was stored at 4°C.

[0037] Example 3: Determination of broad-spectrum antibacterial activity of Streptomyces globosum fermentation broth using the microdilution method Indicator bacterial suspensions were prepared by separately preparing Bacillus subtilis and Escherichia coli suspensions, and adjusting their final concentrations to 1×10⁻⁶. 5 CFU / mL. Spore suspensions of yeast and Fusarium graminearum were prepared separately, and their final concentrations were adjusted to 1×10⁻⁶. 4 Spores / mL; Add 100 µL of the fermentation product sample to be tested to each well of a sterile 48-well plate, followed by 900 µL of the corresponding indicator culture medium (MH medium for Bacillus subtilis and Escherichia coli, YPDA medium for yeast, and RPMI 1640 medium for Fusarium graminearum); A control group was also set up. (a) Positive control (growth control): 100 µL of sterile culture medium (in place of fermentation product) and 900 µL of indicator bacterial suspension were added to each well; (b) Blank control (background control): 100 µL of the fermentation product sample to be tested and 900 µL of sterile culture medium were added to each well to eliminate the background of the culture medium. (c) Negative control (sterile control): 1000 µL of sterile culture medium was added to each well.

[0038] 48-well plates inoculated with bacteria were fermented at 30°C for 24 hours, and 48-well plates inoculated with fungi were fermented at 25°C for 48 hours. After fermentation, the absorbance (OD) of each well was measured at 600 nm using a microplate reader. 600 The inhibition rate is calculated using the following formula: Inhibition rate (%) = [1 - (OD)] / (OD) 样品 -OD 空白对照 ) / (OD 阳性对照 -OD 阴性对照 ×100%. The results are shown in Table 1.

[0039] Table 1. Statistical table of antibacterial rates of metabolite compositions of *Streptomyces flocculationensis* cultured on 10 different culture media.

[0040] (Note: The influence of blank culture medium has been deducted in the antibacterial test.) Data show that culture media 2, 4, and 5 exhibit strong broad-spectrum antibacterial activity.

[0041] Example 4: Fermentation broth of *Streptomyces globosum* with characteristic antibacterial activity and its preparation method (1) Preparation of Streptomyces globosum fermentation broth with antibacterial activity The *Streptomyces circinus* strain was inoculated into 1L shake flasks, each containing 500mL of optimal culture medium (medium ②). Fermentation was carried out at 30℃, 180rpm, and in the dark for 7 days with shaking. All fermentation broth was collected, and mycelia were removed by centrifugation or filtration. The fermentation supernatant was concentrated under reduced pressure and loaded onto an adsorption resin (AB-8 type macroporous adsorption resin). After adsorption, the elution was performed sequentially with pure water and ethanol solutions with volume fractions of 20%, 40%, 60%, 80%, and 100%, for a total elution column volume of three. After concentration under reduced pressure, the samples were freeze-dried to obtain powder samples of each active metabolite.

[0042] (2) Paper disc diffusion method for determining the activity of inhibiting Streptomyces globosum fermentation broth The lyophilized powders of each active metabolite collected by elution with pure water, 20%, 40%, 60%, 80%, and 100% ethanol were reconstituted with 50% methanol-water to a concentration of 10 mg / mL as the test samples. The inhibitory activity of each component was determined using the disk diffusion method. First, indicator agar plates were prepared by melting LB agar, YPDA agar, and PDA agar separately and cooling them to 45-50°C for later use. Add a suspension of Bacillus subtilis or Escherichia coli to melted LB agar, mix well, and pour into plates to achieve a final bacterial concentration of 1 × 10⁻⁶. 6 CFU / mL; Add the yeast suspension to the melted YPDA agar, mix well, and pour into plates to achieve a final bacterial concentration of 1×10⁻⁶. 6 CFU / mL; Add the Fusarium graminearum spore suspension to the melted PDA agar, mix well, and pour into plates to achieve a final spore concentration of 1×10⁻⁶. 5 Spores / mL.

[0043] After all indicator bacteria plates solidified, several sterile filter paper discs with a diameter of 6 mm were aseptically placed on the plate surface. 20 µL of the test sample solution was added dropwise to each filter paper disc, and 20 µL of 50% (v / v) methanol aqueous solution was used as a negative control. All plates were incubated in a 25°C incubator for 2 days, and the diameter (mm) of the inhibition zone was recorded by photograph. The experiment was performed in triplicate.

[0044] The results are as follows Figure 3-4 As shown, the 20% and 40% ethanol eluents exhibited stronger inhibitory effects against Bacillus subtilis and Escherichia coli. The results are as follows... Figure 5-6As shown, the 60%-80% ethanol eluent exhibited stronger inhibitory effects on the antifungal activity against yeast and Fusarium graminearum. In summary, this preparation method successfully achieved the enrichment of compositions that inhibit bacteria and fungi.

[0045] (3) Isolation and identification of Partricin B - UPLC-MS / MS analysis of antibacterial active components The 60% and 80% ethanol eluents were removed from the solution using a rotary evaporator, reconstituted, and the insoluble fractions were washed with water and methanol to obtain a solid sample. This solid sample was then dissolved in DMSO and analyzed for antifungal components using ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS). The analysis was performed using a SCIEX TripleTOF 5600+ hybrid quadrupole-time-of-flight mass spectrometer (manufacturer: AB Sciex Instruments), equipped with a Waters ACQUITY UPLC system. The chromatographic conditions were as follows: a Waters ACQUITY UPLC BEH C column was used. 18 The chromatographic column was 150 mm × 2.1 mm, 1.7 µm; the column temperature was 45.0 ℃; mobile phase A was 0.1% formic acid aqueous solution, and mobile phase B was 0.1% formic acid acetonitrile solution; the flow rate was 0.3 mL / min; and the injection volume was 3.0 µL. The elution gradient was as follows: From 0 to 13.00 min, 5.0% B increased linearly to 50.0% B; From 13:00 to 17:00 min, 50.0% B increased linearly to 95.0% B; 17:00-21:00 min, maintain 95.0% B; From 21:00 to 22:00, the 95.0% B decreased to 5.0% B; 22.00-25.00 min, maintain 5.0% B.

[0046] The UV detection wavelengths were set to 210 nm and 254 nm. Mass spectrometry conditions were as follows: ion source was a Duo Spray ion source; information-dependent acquisition (IDA) mode was used, with scanning performed in both positive and negative ion modes. The baseline chromatogram and primary and secondary mass spectra are shown below. Figure 8 Analysis revealed that the main component of this antibacterial agent was partricin B, comprising 80% of the composition. Its structural formula is shown below. Figure 7 .

[0047] The above description is only a partial embodiment of the present invention and is not intended to limit the present invention. 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 strain of Streptomyces globiceps ZJU704, characterized in that, The classification name is Streptomyces globosus (ATCC 27438) Streptomyces globosus and the preservation number is CGMCC NO. 36895, which is preserved in the General Microbiological Center of China Microorganism Culture Collection Committee, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Yard, West Beichen Road, Chaoyang District, Beijing, on December 4, 2025.

2. Streptomyces globiceps ZJU704 according to claim 1, characterized in that, The culture is carried out using any one of the following fermentation media: (a) yeast extract 3-5 g / L, starch 5-15 g / L, proteose peptone 1-3 g / L, mannitol 3-5 g / L, sea salt 30-35 g / L, pH 7.3-7.5; (b) glucose 5-15 g / L, corn steep liquor 5-15 g / L, soybean meal 5-15 g / L, glycerol 3-7 g / L, dry yeast 3-7 g / L, NaCl 3-7 g / L, CaCO3 1-3 g / L, pH 5.6-5.8; (c) soluble starch 5-15 g / L, glucose 5-15 g / L, proteose peptone 6-8 g / L, yeast extract 1-3 g / L, glycerol 5-15 g / L, corn extract 2-3 g / L, sea salt 30-35 g / L, CaCO3 2-4 g / L, pH 6.8-7.

2.

3. A fermentation process of Streptomyces glomeratus, characterized by, The method employs Streptomyces globiceps ZJU704 of claim 1 ( Streptomyces globosus ZJU704), comprising the following steps: (a) inoculating the Streptomyces globosus into the medium of claim 2 to carry out fermentation; (b) after the fermentation is completed, separating and purifying the fermentation broth to obtain a supernatant containing antibacterial activity.

4. The fermentation process of claim 3, wherein, In step (a), the inoculation amount of the S. globosa is 10 5 CFU / mL 7 CFU / mL And / or, the fermentation conditions of the Streptomyces globosus are: 28-32°C, 150-200 rpm, and 5-9 days of shaking culture in the dark.

5. The fermentation process of claim 3, wherein, In step (b), the separation and purification include: adsorbing the fermentation broth on a macroporous resin, eluting with a gradient of ethanol with a volume fraction of 20%-100%, an elution volume of 1-5 column volumes, and collecting the eluate.

6. The fermentation process of claim 3, wherein, The macroporous resin is AB-8 type macroporous resin. And / or, the volume fraction of the ethanol solution is 60%. And / or, the elution volume is 3 column volumes.

7. A biological bacteriostatic agent, characterized by, The biological antibacterial agent is prepared by the method of any one of claims 3-6.

8. The biological bacteriostatic agent of claim 7, wherein, The effective antibacterial component of the biological antibacterial agent includes partricin B.

9. Use of a biocide according to claim 7 or 8 for the inhibition of microorganisms, characterized in that, The microorganism is selected from at least one of the following: A1) Bacillus subtilis; A2) Escherichia coli; A3) yeast; A4) Fusarium graminearum; The Bacillus subtilis is preferably Bacillus subtilis 3610; the Escherichia coli is preferably Escherichia coli DH5α; the yeast is preferably yeast BY4741; and the Fusarium graminearum is preferably Fusarium graminearum PH-1.

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