CN115109023A - Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof - Google Patents
Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/22—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom rings with more than six members
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/08—Oxygen as only ring hetero atoms containing a hetero ring of at least seven ring members, e.g. zearalenone, macrolide aglycons
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Abstract
The invention belongs to the technical field of microorganisms and novel medicines and pesticides, and particularly relates to a novel macrolide compound FWYZ52-A and application thereof, and further discloses a micromonospora marinensis capable of fermenting the compound, and a method for preparing the macrolide compound FWYZ52-A by fermenting based on a strain. The macrolide compound FWYZ52-A is a novel structural substance and has inhibitory activity on staphylococcus aureus in bacteria. The marine Micromonospora sp FIMYZ52 with the inhibitory activity on bacteria and oxidation resistance separated and screened by the invention can be used for preparing a macrolide compound FWYZ52-A with the inhibitory activity on staphylococcus aureus by fermentation.
Description
Technical Field
The invention belongs to the technical field of microorganisms and novel medicines and pesticides, particularly relates to a novel macrolide compound FWYZ52-A and application thereof, and further discloses micromonospora marinensis capable of fermenting the compound and a method for preparing the macrolide compound FWYZ52-A by fermenting based on a strain.
Background
Micromonospora (Micromonospora) belongs to the family Micromonosporaceae (Micromonosporaceae) of the order Actinomycetales, and its strains are widely available, both from freshwater lakes and isolated from marine environments. By 2016, Talukdar et al, there were nearly 700 antibiotics from Micromonospora metabolites. Therefore, the Micromonospora parvum is an important treasury of bioactive secondary metabolites (Qi et al, 2020), and has important significance for developing various novel antibiotic drugs.
It has been reported that micromonospora can produce a wide variety of active substances, and among them, macrolide substances produced by micromonospora include Levantilide A and Levantilide C which exhibit moderate anti-malignant cell proliferation activities against various tumor cells, such as human leukemia tumor (HL-60), human breast tumor (MDA-MB-231), human colon cancer (SW620) and human liver cancer (SMMC7721), bafilomycin which can be used as an insecticide for inhibiting the growth of malignant cells, Rosamicin which has a broad-spectrum antibacterial activity, and juvenimicin C which can enhance the activity of QR1 enzyme and the folding level of glutathione. In 2011, Johannes F.Imhoff et al found novel macrolide compounds Levantilide A and Levantilide B from metabolites of Micromonospora sp.Strain M71-A77, which have moderate degrees of anti-proliferation activity against various tumor cells, from deep sea environment; a macrolide compound Levantilide C with a novel structure is found in a metabolite of micromonospora marinensis FIM07-0019 by Pengfei et al in 2013, and also has the anti-proliferation activity on various tumor cells. However, no report has been found that the Levantilides compounds have antibacterial activity.
Therefore, the novel macrolide active substances are mined from the metabolites of micromonospora, so that the method is beneficial to continuously expanding the current drug storage library and provides guarantee for the healthy life of human beings.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide a novel macrolide compound FWYZ52-A, wherein the compound FWYZ52-A has antibacterial property against staphylococcus aureus;
the second technical problem to be solved by the invention is to provide a marine micromonospora strain, which can be used for producing the macrolide compound FWYZ52-A through fermentation;
the third technical problem to be solved by the invention is to provide a method for preparing the macrolide compound FWYZ52-A based on the fermentation of the marine micromonospora strain;
the fourth technical problem to be solved by the present invention is to provide the use of the macrolide compound FWYZ 52-a.
In order to solve the technical problem, the invention provides a macrolide compound FWYZ52-A, which has a structure shown as the following formula (I):
the invention also discloses a marine Micromonospora strain FIMYZ52 which is classified and named as actinomycete Micromonospora sp and is preserved in China general microbiological culture collection center on 3, 7 and 2022 months, wherein the preservation number is CGMCC No. 24479.
The invention also discloses application of the marine micromonospora strain in fermentation preparation of the macrolide compound FWYZ 52-A.
The invention also discloses a method for preparing the macrolide compound FWYZ52-A, which comprises the step of inoculating the marine micromonospora strain into a suitable fermentation medium for fermentation culture.
Specifically, the preparation method of the macrolide compound FWYZ52-A comprises the following steps:
(1) inoculating Micromonospora sp (Micromonospora sp.) FIMYZ52 stored on a slant into a liquid seed culture medium for constant-temperature culture, and collecting seed liquid for later use;
the liquid seed culture medium comprises the following components: 1-2 wt% of soluble starch, 0.1-1 wt% of glucose, 0.1-1 wt% of yeast extract and MgSO 4 ·7H 2 O 0.01-0.1wt％，NaCl 0.01-0.1wt％， (NH 4 ) 2 SO 4 0.01-0.1wt％，CaCO 3 0.05-0.2wt％，pH 6.0-8.5；
Preferably, the components of the liquid seed culture medium include: 1.5 wt% of soluble starch, 0.5 wt% of glucose, 0.5 wt% of yeast extract and MgSO 4 ·7H 2 O 0.05wt％，NaCl 0.05wt％， (NH 4 ) 2 SO 4 0.05wt％，CaCO 3 0.1wt％，pH 6.0-8.5；
(2) Transferring the seed liquid to a fermentation culture medium for constant temperature culture to obtain fermentation liquid containing the needed macrolide compound FWYZ 52-A;
the components of the fermentation medium comprise: 3-5 wt% of soluble starch, 0.1-1 wt% of glucose, 2-3 wt% of soybean cake powder, 0.1-1 wt% of yeast powder and MgSO 4 ·7H 2 O 0.01-0.1wt％、K 2 HPO 4 0.01- 0.1wt％、CaCO 3 0.05-0.2 wt% and distilled water, and the pH is 6.0-8.5;
preferably, the components of the fermentation medium include: 4 wt% of soluble starch, 0.5 wt% of glucose, 2.5 wt% of soybean cake powder, 0.5 wt% of yeast powder and MgSO 4 ·7H 2 O 0.05wt％、K 2 HPO 4 0.05wt％、 CaCO 3 0.1 wt% and distilled water, and the pH value is 6.0-8.5.
Specifically, the preparation method of the macrolide compound FWYZ52-A comprises the following steps:
in the step (1), the temperature of the culture step is 25-35 ℃, and the culture time is 2-3 days;
in the step (2), the temperature of the culture step is 25-35 ℃, and the culture time is 3-5 days.
Specifically, the preparation method of the macrolide compound FWYZ52-A further comprises the steps of extracting and purifying the macrolide compound FWYZ52-A, and specifically comprises the following steps:
extraction: performing solid-liquid separation on the collected fermentation liquor and mycelium, wherein the fermentation liquor is adsorbed by macroporous resin HP20, and a crude extract A is obtained after the adsorption, the ethanol desorption, the recovery and the concentration; extracting the mycelium by an alcohol solvent, collecting an extracting solution, and concentrating under reduced pressure to obtain a crude extract B;
and (3) purification: and (3) combining the crude extract A and the crude extract B, and purifying by adopting normal phase silica gel column chromatography, wherein the volume ratio is 10: 0-0: 10, carrying out gradient elution by using a petroleum ether-ethyl acetate solvent, detecting by using thin layer chromatography, and collecting an eluent containing the macrolide compound FWYZ 52-A; then, the meridian C 18 Performing reverse phase column chromatography, performing gradient elution with 50-95% methanol-water solution by volume ratio, detecting by high performance liquid chromatography, and collecting eluate containing compound FWYZ 52-A; then prepared to form C 18 Performing reverse phase high pressure liquid chromatography, and performing gradient elution with 50-60% methanol-water solution to obtain pure macrolide compound FWYZ 52-A.
Specifically, the mass ratio of the macroporous resin HP20 to the fermentation liquor is 1: 10-1: 30, adsorbing the mixture by a resin column, washing the adsorbed mixture by distilled water, removing impurities by 10-20% ethanol, desorbing by 100% ethanol, and recovering ethanol solvent to obtain a crude extract A of FW YZ 52; extracting mycelium with ethanol or methanol for 3 times, and concentrating the soaking solution under reduced pressure to obtain extract B.
The invention also discloses application of the daphnoretin compound FWYZ52-A in preparing medical, veterinary or agricultural antibacterial preparations for non-therapeutic purposes.
Specifically, the antibacterial preparation comprises a staphylococcus aureus bacteriostatic agent.
The macrolide compound FWYZ52-A provided by the invention has a 20-membered ring and a macrolide antibiotic containing a hydroxyl short fatty chain, is a novel structural substance, has an inhibitory activity on staphylococcus aureus in bacteria through verification, provides a lead compound for researching and developing a new Levantilides series active drug, and has an important value for developing and utilizing Chinese marine drug resources.
The invention separates and screens a marine Micromonospora sp (Micromonospora sp.) FIMYZ52 with antibacterial property from marine actinomycetes, and can be used for preparing a macrolide compound FWYZ52-A with inhibitory activity against staphylococcus aureus by fermentation.
According to the preparation method of the macrolide compound FWYZ52-A, disclosed by the invention, fermentation is carried out based on Micromonospora sp FIMYZ52, and a macrolide compound FWYZ52-A pure product is obtained through fermentation liquor extraction and purification, so that the fermentation efficiency and the extraction efficiency are ideal.
Drawings
In order that the present disclosure may be more readily and clearly understood, the following detailed description of the present disclosure is provided in connection with specific embodiments thereof and the accompanying drawings, in which,
FIG. 1 is a schematic diagram of a phylogenetic tree of a Micromonospora marinum strain according to the present invention based on the 16S rRNA gene sequence;
FIG. 2 is a high resolution mass spectrum of FWYZ52-A of the macrolide compound of the present invention;
FIG. 3 is a hydrogen nuclear magnetic resonance image of FWYZ52-A macrolide compound of the present invention 1 H spectrum;
FIG. 4 is a carbon nuclear magnetic resonance image of FWYZ52-A macrolide compound of the present invention 13 C spectrum;
FIG. 5 is a drawing showing FWYZ52-A macrolide compounds of the present invention 1 H- 1 HCOSY spectra;
FIG. 6 is an HSQC-related plot of the macrolide compound FWYZ52-A of the present invention;
FIG. 7 is a HMBC spectrum of FWYZ52-A of a macrolide compound of the invention.
Detailed Description
The invention obtains a strain of Micromonospora sp (Micromonospora sp.) FIMYZ52 from sea through screening, the Micromonospora sp belongs to Micromonospora in actinomycetes through 16S rRNA gene analysis, and in addition, a macrolide compound FWYZ52-A with a novel structure and inhibitory activity to staphylococcus aureus in bacteria is obtained by extracting and separating from Micromonospora sp 52 fermentation liquor.
Example 1 identification of Strain FIMYZ52
Extracting the screened Micromonospora sp.FIMYZ52 genome DNA by an enzymolysis method, storing the obtained DNA sample at-20 ℃, performing 16S rRNA gene PCR amplification by taking the DNA sample as a DNA template, and externally sequencing the PCR product.
The schematic diagram of the phylogenetic tree of the micromonospora marinensis strain based on the 16S rRNA gene sequence is shown in figure 1. Performing blast comparison on the 16S rDNA sequence of the tested strain and the existing sequence in a GenBank database, and performing homology analysis. The result is 96.93 percent of similarity with Micromonospora sp; the accession number is: KP900787.1, 16S partial sequence total length 1454bp, the concrete sequence is shown in SEQ ID No. 1.
The strain FIMYZ52 is judged to be a Micromonospora, is classified and named as actinomycetes Micromonospora sp, is stored in China general microbiological culture collection center of China Committee for culture Collection of microorganisms 3-7 days 2022, and has a storage address of No. 3 Siro-1 Hospital in the sunward area of Beijing, and a storage number of CGMCC No. 24479.
EXAMPLE 2 fermentative preparation of macrolide Compound with New Structure FWYZ52-A
Inoculating the screened Micromonospora sp.FIMYZ52 of the marine Micromonospora into ISP2 agar slant culture, inoculating into a liquid seed culture medium, culturing at the temperature of 30 ℃ for 2 days, and then mixing the seeds with the artificial seed culture medium according to the volume ratio of 1: 10 at 30 deg.C, shaking for 4 days, and collecting the fermentation product.
The seed culture medium comprises the following components: 1.5 wt% of soluble starch, 0.5 wt% of glucose, 0.5 wt% of yeast extract and MgSO 4 ·7H 2 O 0.05wt％、NaCl 0.05wt％、(NH 4 ) 2 SO 4 0.05wt％、 CaCO 3 0.1 wt%, prepared with distilled water, pH 6.0-8.5;
the selected fermentation medium comprises the following components: 4 wt% of soluble starch, 0.5 wt% of glucose, 2.5 wt% of soybean cake powder, 0.5 wt% of yeast powder and MgSO 4 ·7H 2 O 0.05wt％、K 2 HPO 4 0.05wt％、 CaCO 3 0.1 wt%, distilled water, and pH 6.0-8.5.
And (2) performing solid-liquid separation on the fermentation liquor and the mycelia, adsorbing the fermentation liquor by using macroporous resin HP20, and mixing the resin and the fermentation liquor according to the mass ratio of 1: 20, mixing, adsorbing by a resin column, washing by distilled water after adsorption, removing impurities by 10-20% ethanol, desorbing by 100% ethanol, and recovering a crude extract A of a compound FWYZ52-A after ethanol solvent recovery; extracting mycelium with ethanol or methanol for 3 times, and concentrating the soaking solution under reduced pressure to obtain extract B.
And (2) combining the crude extract A and the crude extract B, and separating by adopting normal-phase silica gel column chromatography and reverse-phase C18 column chromatography, wherein the crude extracts are prepared from petroleum ether: gradient eluting with ethyl acetate solvent (volume ratio of 10: 0-0: 10), detecting by thin layer chromatography, and collecting eluate containing macrolide compound FWYZ 52-A; then through C 18 Reversed phase column chromatography, eluting with methanol: eluting with water (50-95 vol.%), detecting by HPLC, and collecting substance containing FWYZ 52-A; through preparation type C 18 Reverse phase high pressure liquid chromatography (methanol water 50-60%) gradient elution, concentrating and evaporating to dryness 60% methanol water section to obtain pure macrolide compound FWYZ52-A with antibacterial activity.
Example 3 structural analysis of the Compound FWYZ52-A
A macrolide compound having a novel structure is isolated from the fermentation broth of the novel strain, and the structure of the macrolide compound FWYZ52-A is identified by MS and NMR techniques.
The large ringThe physical and chemical properties of the lactone compounds FWYZ52-A are brown amorphous solids, and the molecular formula is as follows: c 30 H 50 O 7 High resolution mass spectrometry: measurement values: m/z 545.3492[ M + Na ]] + Theoretical value M/z 545.3449[ M + Na ]] + The unsaturation degree is 6. Solubility: can be dissolved in organic solvents such as methanol, acetonitrile, ethyl acetate and dimethyl sulfoxide.
Of FWYZ52-A 1 H nmr spectrum (DMSO-d6, 600MHz) δ 7.06(dd, J ═ 15.2,10.9Hz,1H),6.31(dd, J ═ 16.3,10.9Hz,1H),6.12(ddd, J ═ 14.9,9.0,5.5 Hz,1H),5.77(d, J ═ 15.3Hz,1H),4.74(d, J ═ 7.6Hz,2H),4.71(d, J ═ 6.5, 2H),3.95(d, J ═ 7.4Hz,2H),3.92(s,1H),3.82(dt, J ═ 9.1,4.0Hz,1H),2.95(d, J ═ 7.5, 1H), 2.56-2.51 (m,1H), 1.51 (t, J ═ 9.1, 4.5H), 1H, 2.95(d, J ═ 7.5, 1H), 2.56-2.51H, 1, 5 (t, 1.5H, 1H, 6.5H, 1, 6.5H, 6H, 1H, 6H, 1H, 6H, 1H, 6H, 5H, 6H, 1H, 5H, 6H, 1H, 5H, 1H, 5H, 6H, 1H, 5H, 1H, 6H, 1H, 1H, 5, 6H, 1H, 6H, 1H, 6H, 1H, 5, 1H, 5H, 1H, 6H, 1H, 5H, 1H, 6H, 1H, 6H, 1H, 1H, 1H, 1, 6, 1H, 6, 1, 5,6, 1H, 1H, 1, 1H) 1.04(s,3H),0.90(t, J ═ 7.3Hz,3H), 0.87(d, J ═ 7.0Hz,3H),0.83(d, J ═ 6.7Hz,3H),0.54(d, J ═ 6.4Hz, 3H).
Of FWYZ52-A 13 C nuclear magnetic resonance spectrum (DMSO-D6, 150MHz): 13 C NMR(151 MHz,DMSO)δ210.8,166.3,144.3,140.7,133.8,132.5,130.3,119.7,78.0,77.6, 77.1,70.9,67.1,41.4,41.3,41.1,41.0,40.0,35.0,34.1,33.5,31.3,30.1,29.0, 21.2,20.2,20.1,18.7,16.3,7.7。
meanwhile, the invention also determines various nuclear magnetic resonance spectra of the compound FWYZ52-A, which are shown in the attached figures 2-7 in detail, thereby determining the attribution of all carbon atoms and hydrogen atoms of the compound and the chemical structure of the compound, determining the compound as a macrolide compound with a novel structure, and the structural formula is characterized as shown in the following table 1.
TABLE 1 preparation of FWYZ52-A compounds 1 H and 13 c (DMSO-6) attribution
In conclusion, the structural formula of the compound FWYZ52-A obtained by extraction and purification is as follows:
EXAMPLE 4 macrolide Compounds FWYZ52-A antibacterial Activity assay
In this example, a bacterial and fungal inhibition test in vitro was performed on the macrolide compound FWYZ52-A, and the bacterial and bacterial inhibition activity of the compound FWYZ52-A was determined by a paper-agar diffusion test (paper-agar disk diffusion assay), which indicates that the compound FWYZ52-A has the effect of inhibiting the bacterium Staphylococcus aureus.
Firstly, 10 portions of colibacillus and staphylococcus aureus are added -8 Density of colonies per ml was poured onto MH plates; candida albicans, Aspergillus niger 10 -8 Spore density per ml was inverted to saxifrage plates. And (3) dissolving FWYZ52-A in a methanol solution, placing 8 mu l of a sample to be tested on a circular filter paper sheet with the diameter of 6mm, sticking the filter paper sheet carrying the sample on a test bacterium (escherichia coli, staphylococcus aureus, candida albicans and aspergillus niger) plate with the concentration after the methanol on the filter paper sheet completely emits, and simultaneously, taking the methanol solution as a negative control and culturing at the constant temperature of 28 ℃ for 24-48 hours. Observing and recording the diameter of the inhibition zone, wherein the larger the diameter of the inhibition zone is, the stronger the antibacterial activity of the strain is.
Experimental results show that the macrolide compound FWYZ52-A has antibacterial activity against staphylococcus aureus, and the diameter of a bacteriostatic circle is 7-8 mm. Therefore, the compound FWYZ52-A is expected to be a lead compound for antibacterial activity.
In conclusion, the in vitro bacterial activity inhibition test of the macrolide compound shows that the compound FWYZ52-A has the activity of inhibiting staphylococcus aureus, thereby providing a lead compound for researching and developing new bacteria inhibition medicaments and having important value for developing and utilizing marine medicament resources in China.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (10)
1. A macrolide compound FWYZ52-A, characterized in that the compound has the following structure shown in formula (I):
2. a marine Micromonospora strain FIMYZ52 is classified and named as Micromonospora sp, which is deposited in China general microbiological culture Collection center on 3-7.2022 years, and the deposit number is CGMCC No. 24479.
3. Use of a micromonospora marinum strain according to claim 2 for the fermentative preparation of macrolide compound FWYZ52-a according to claim 1.
4. A process for preparing the macrolide compound FWYZ52-A according to claim 1, which comprises the step of inoculating the Micromonospora marinum strain of claim 2 in a suitable fermentation medium for fermentation culture.
5. A process for the preparation of macrolide compounds FWYZ52-A according to claim 4, characterized in that it comprises the following steps:
(1) inoculating Micromonospora sp.FIMYZ52 of Micromonospora stored on a slant into a liquid seed culture medium for constant-temperature culture, and collecting seed liquid for later use;
the components of the liquid seed culture medium comprise: soluble in water1-2 wt% of native starch, 0.1-1 wt% of glucose, 0.1-1 wt% of yeast extract and MgSO 4 ·7H 2 O 0.01-0.1wt％，NaCl 0.01-0.1wt％，(NH 4 ) 2 SO 4 0.01-0.1wt％，CaCO 3 0.05-0.2wt％，pH 6.0-8.5；
(2) Transferring the seed liquid to a fermentation culture medium for constant temperature culture to obtain fermentation liquid containing the needed macrolide compound FWYZ 52-A;
the components of the fermentation medium comprise: 3-5 wt% of soluble starch, 0.1-1 wt% of glucose, 2-3 wt% of soybean cake powder, 0.1-1 wt% of yeast powder and MgSO 4 ·7H 2 O 0.01-0.1wt％、K 2 HPO 4 0.01-0.1wt％、CaCO 3 0.05-0.2 wt% and distilled water, and the pH value is 6.0-8.5.
6. A process for the preparation of macrolide compounds FWYZ52-A according to claim 5, characterized in that:
in the step (1), the temperature of the culture step is 25-35 ℃, and the culture time is 2-3 days;
in the step (2), the temperature of the culture step is 25-35 ℃, and the culture time is 3-5 days.
7. A process for the preparation of the macrolide compound FWYZ52-A according to any of claims 4 to 6, further comprising the steps of extraction and purification of the macrolide compound FWYZ52-A, in particular comprising:
extraction: performing solid-liquid separation on the collected fermentation liquor and mycelium, wherein the fermentation liquor is adsorbed by macroporous resin HP20, and a crude extract A is obtained after the adsorption, the ethanol desorption, the recovery and the concentration; extracting the mycelium by an alcohol solvent, collecting an extracting solution, and concentrating under reduced pressure to obtain a crude extract B;
and (3) purification: and (3) combining the crude extract A and the crude extract B, and purifying by adopting normal-phase silica gel column chromatography, wherein the volume ratio of the crude extract A to the crude extract B is 10: 0-0: 10, carrying out gradient elution by using a petroleum ether-ethyl acetate solvent, detecting by using thin layer chromatography, and collecting an eluent containing the macrolide compound FWYZ 52-A; then, the meridian C 18 Performing reverse phase column chromatography, performing gradient elution with 50-95% methanol-water solution by volume ratio, detecting by high performance liquid chromatography, and collecting eluate containing compound FWYZ 52-A; then prepared to form C 18 Performing reverse phase high pressure liquid chromatography, and performing gradient elution with 50-60% methanol-water solution to obtain pure macrolide compound FWYZ 52-A.
8. The preparation method of the macrolide compound FWYZ52-A according to claim 7, wherein the mass ratio of the macroporous resin HP20 to the fermentation broth is 1: 10-1: 30.
9. use of macrolide compound FWYZ52-a according to claim 1 for the preparation of antibacterial formulations for medical, veterinary or agricultural non-therapeutic purposes.
10. The use according to claim 9, wherein the antibacterial formulation comprises a staphylococcus aureus bacteriostatic agent.
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