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Application of novel secondary metabolite LW-4 of aspergillus terreus SKL-001

A secondary metabolite, LW-4 technology, applied in the field of medicine, can solve the problem of not obvious inhibitory activity of Gram-negative bacteria, achieve the effect of improving the extraction rate of fermentation products and accelerating the release of intracellular substances

Inactive Publication Date: 2019-01-04
ZHEJIANG OCEAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The isolated compound has a strong inhibitory effect on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and has a certain inhibitory effect on Gram-negative bacteria. The minimum inhibitory concentration MIC is less than 12.5μM, indicating that it can be developed into a potential antibacterial drug, but the inhibitory activity of the fungal secondary metabolite derivatives from Liushan Lake on Gram-negative bacteria is not obvious

Method used

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  • Application of novel secondary metabolite LW-4 of aspergillus terreus SKL-001
  • Application of novel secondary metabolite LW-4 of aspergillus terreus SKL-001
  • Application of novel secondary metabolite LW-4 of aspergillus terreus SKL-001

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Embodiment 1

[0020] The purposes of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the new secondary metabolite LW-4 is the compound shown in formula I, its stereoisomer or pharmaceutically accessible salt, the chemical structure formula is :

[0021]

[0022] The application of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the preparation method of the new secondary metabolite LW-4 includes strain fermentation, secondary metabolite extraction and separation and purification, the specific steps are:

[0023] Strain fermentation: add the epigenetic modification regulator SAHA to the fungal medium with a final concentration of 15 μM, 0.05% paricalcitol, 0.1% triglyceride, stir evenly, let stand, and ferment for 30 days; Paricalcitol Calciferol and triglyceride are added to the fungal culture medium, which can act synergistically with the epigenetic modification regulator SAHA to change the dissolved oxygen environment in the culture medium, promote m...

Embodiment 2

[0027] The purposes of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the new secondary metabolite LW-4 is the compound shown in formula I, its stereoisomer or pharmaceutically accessible salt, the chemical structure formula is :

[0028]

[0029] The use of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the preparation method of the new secondary metabolite LW-4 includes strain fermentation, secondary metabolite extraction and separation and purification, the specific steps are:

[0030] Strain fermentation: add the epigenetic modification regulator SAHA to the fungal culture medium with a final concentration of 10 μM, 0.08% paricalcitol, and 0.1% triglyceride, stir evenly, let stand, and ferment for 30 days;

[0031] Extraction of secondary metabolites: After the fermentation is completed, separate the mycelium and the fermentation broth with silk cloth; add an equal volume of ethyl acetate to the fermentation broth and stir and extra...

Embodiment 3

[0034]The purposes of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the new secondary metabolite LW-4 is the compound shown in formula I, its stereoisomer or pharmaceutically accessible salt, the chemical structure formula is :

[0035]

[0036] The application of the new secondary metabolite LW-4 of Aspergillus terreus SKL-001, the preparation method of the new secondary metabolite LW-4 includes strain fermentation, secondary metabolite extraction and separation and purification, the specific steps are:

[0037] Strain fermentation: add the epigenetic modification regulator SAHA to the fungal medium, the final concentration is 10 μM, 0.1% paricalcitol, 0.15% triglyceride, stir evenly, let stand, ferment for 30 days, and ferment together 60L; adding paricalcitol and triglycerides to the fungal culture medium can increase the dissolved oxygen in the culture medium, reduce the interfacial tension and prevent the bacteria from attaching to the air bubbles, ...

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Abstract

The invention discloses application of a novel secondary metabolite LW-4 of aspergillus terreus SKL-001. The novel secondary metabolite LW-4 is prepared by steps: adding an epigenetic modification regulating agent SAHA, paricalcitol and triglyceride into a fungal culture medium, performing fermentation culture, adopting ethyl acetate and 80% acetone-water for extracting fermentation liquor and mycelia respectively, and subjecting fermentation concentrate to column chromatography and thin-layer chromatography separation and purification to obtain the novel secondary metabolite LW-4. The epigenetic modification regulating agent SAHA is adopted for epigenetic modification of aspergillus terreus SKL-001 to obtain the novel secondary metabolite LW-4 through separation. The secondary metaboliteLW-4 of aspergillus terreus SKL-001 has great escherichia coli inhibiting activity, has a minimum inhibition concentration of 15microgram / mL and can be potentially developed for preparation of pharmaceutical preparations resistant to Gram-negative bacteria.

Description

technical field [0001] The invention relates to the field of medicines, in particular to a preparation method and application of a new secondary metabolite LW-4 of Aspergillus terreus SKL-001 which can be used as an antibacterial agent. Background technique [0002] As we all know, microorganisms have long been an important source of active substances such as antibiotics and enzyme inhibitors. Microorganisms have become a hotspot in the field of natural product research due to their large-scale fermentation and cultivation, no raw material restrictions, and no environmental damage. In recent years, the probability of obtaining new compounds from terrestrial microorganisms has been greatly reduced. However, due to the specific living environment of marine-derived microorganisms, in addition to producing metabolites similar to those on land, sometimes some new compounds with specific structures can also be produced, showing a huge development and utilization prospects. Asper...

Claims

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Application Information

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IPC IPC(8): A61K31/5025C07D487/04C12P17/18A61P31/04C12R1/66
CPCA61K31/5025A61P31/04C07D487/04C12P17/182Y02A50/30
Inventor 孙坤来张译文王斌初学梅梁丽丽陈荫赵玉勤
Owner ZHEJIANG OCEAN UNIV
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