PKS type-I polyketones compound with immunosuppression activity and preparation method and application of PKS type-I polyketones compound

A polyketide compound, immunosuppressive technology, applied in the field of medicine and biology, can solve the problems of high price, hyperlipidemia, inducing tumors, etc., and achieve the effect of low price

Active Publication Date: 2019-03-15
HAINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The immunosuppressive drugs clinically used to treat autoimmune diseases and transplant rejection mainly include cyclosporin A (CsA), tacrolimus (FK506), etc. With different degrees of liver and kidney toxicity or neurotoxicity, long-term use can cause hyperlipidemia, metabolic bone disease and even induce tumors; at the same time, these immunosuppressive drugs are also relatively expensive

Method used

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  • PKS type-I polyketones compound with immunosuppression activity and preparation method and application of PKS type-I polyketones compound
  • PKS type-I polyketones compound with immunosuppression activity and preparation method and application of PKS type-I polyketones compound
  • PKS type-I polyketones compound with immunosuppression activity and preparation method and application of PKS type-I polyketones compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Cultivation and identification of Streptomyces sp.DSM 4137

[0043] Zeeck first isolated microbial samples Streptomyces sp.DSM 3816 from soil samples in Greece. The strain Streptomyces sp.DSM 4137 is Streptomyces sp. DSM 3816 or its mutants, provided by the University of Cambridge, UK. The strains were grown in SFM medium for 30 Cultivated at a constant temperature at ℃, extensively branched substrate hyphae (0.3-0.5 μm in diameter) and aerial hyphae were formed, which differentiated into compact chains of helical spores. The appearance of the spores ranged from cylindrical to barrel-shaped (1.3-1.0 x 1.5 pm) with a wrinkled surface. The color of the substrate mycelium tends to be brown / gray or yellow / grey. At maturity, the aerial hyphae differentiate into compact, spirally rugose, cylindrical spore chains. For the results of morphological identification, see figure 1 .

Embodiment 2

[0044] Example 2: Optimization of fermentation conditions for Streptomyces sp.DSM 4137

[0045]Take an appropriate amount of strains, inoculate them on SFM solid plane medium (soybean powder 2%, D-mannitol 2%, agar 2%), and cultivate them in a 30°C incubator for 6 days. Pick appropriate spores and thalline with an inoculation needle, inoculate into a 25mL Erlenmeyer flask containing 5mL of TSBY seed culture solution (trypsin soybean broth 3%, sucrose 10.3%, yeast extract 0.5%), and place in a shaker , cultivated at 30° C. and 150 rpm for 48 hours to obtain a seed culture solution.

[0046] Get the seed culture solution (0.2mL), inoculate it on TSBY liquid fermentation medium, SFM liquid fermentation medium, TSBY solid fermentation medium, SFM solid fermentation medium, cultivate 2d, 4d, 6d in 30 ℃ incubator, obtain For the fermentation culture of the strain, HPLC-ESI-MS adopts a 5μC18 column (4.6×250mm, Phenomenex), and the solvent system in Table 1 is used for metabolite scr...

Embodiment 3

[0062] Embodiment three, the separation preparation and structural identification of compound Efophylin B (I)

[0063] 3.1 Extraction of strain fermentation products

[0064] After the 6L SFM solid medium was fermented, it was fully soaked in 2 times the volume of methanol for 2 hours, the methanol extract was obtained by filtration, concentrated under reduced pressure, and the methanol was recovered. This was repeated three times to obtain 36 g of the fermentation product of strain Streptomyces sp.DSM 4137.

[0065] 3.2 Thin layer detection (TLC) rapid identification of Efophylin B

[0066] ① point board

[0067] Take a small amount of fermented extract and dissolve it with a small amount of solvent, and use a capillary to spot on the thin layer of silica gel GF 254 board. The diameter of the spot plate is about 2 mm, and the distance from the thin-layer plate is about 1.5 cm. After pointing the sample, wait for it to evaporate to dryness and put it into the chromatograph...

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Abstract

The invention relates to a PKS type-I polyketones compound Efophylin B with immunosuppression activity and a preparation method and application of the PKS type-I polyketones compound. Streptomyces sp.DSM 4137 is fermented by an SFM solid culture medium, and a fermented product is separated and purified to obtain the compound. Experiments prove that the compound has remarkable calmodulin phosphatase suppression activity, the immunosuppression effect of the compound is higher than that of cyclosporin A as an immunosuppressor used clinically and widely, toxicity to spleen cells is quite weak, andthe PKS type-I polyketones compound is an efficient low-toxicity immunosuppressor, and can be used for preparing a second-generation immunosuppressive drug for organ transplantation and autoimmune diseases.

Description

technical field [0001] The invention relates to a PKS type I polyketide compound with immunosuppressive activity and a preparation method and application thereof, belonging to the field of medical biotechnology. Background technique [0002] Immunosuppressive drugs refer to drugs that have an inhibitory effect on the body's immune response. They are developed for autoimmune diseases. They can inhibit the proliferation and function of cells related to immune responses and reduce the body's immune response. The immunosuppressive drugs clinically used to treat autoimmune diseases and transplant rejection mainly include cyclosporin A (CsA), tacrolimus (FK506), etc. They have varying degrees of liver and kidney toxicity or neurotoxicity, and long-term use can cause hyperlipidemia, metabolic bone disease, and even induce tumors; meanwhile, these immunosuppressive drugs are relatively expensive. Therefore, there is an urgent need to find a low-toxic, effective and inexpensive immu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/04C07H1/06A61P37/06C12P19/60C12R1/465
CPCA61P37/06C07H1/06C07H17/04C12P19/60
Inventor 徐静
Owner HAINAN UNIVERSITY
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