A kind of preparation method of desert pseudocystoid and oritavancin intermediate

A technology of oritavancin and cysts, which is applied in the field of medicine and can solve problems such as small-scale resection and frameshift mutation

Active Publication Date: 2019-09-27
ZHEJIANG HISUN PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mutations induced by NTG are mainly GC-AT transitions, in addition to small excisions, frameshift mutations, and loss of GC pairs

Method used

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  • A kind of preparation method of desert pseudocystoid and oritavancin intermediate
  • A kind of preparation method of desert pseudocystoid and oritavancin intermediate
  • A kind of preparation method of desert pseudocystoid and oritavancin intermediate

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Embodiment 1

[0050] The preparation of embodiment 1 high-yield bacterial strain Cystobasidium deserticus HS807-AN-2396 (Kibdelosporangium aridum)

[0051] The strain A.orientalis A82846 was isolated from soil samples in Haiti (for strain A.orientalisA82846 see: Oliver Puk, Petra Huber, Daniel Bischoff, etc., Glycopeptide Biosynthesis in Amycolatopsis mediterranei DSM5908: Function of a Halogenase and a Haloperoxidase / Perhydrolase, Chemistry & Vol.9, 225–235, February, 2002), and then the HS807-O-13 strain was naturally isolated, and the HS807-O-13 strain was screened by mutagenesis to obtain the starting strain HS807-A-639. The bacterial suspension of HS807-A-639 was prepared and filtered with filter paper, and the cell dispersion degree of microscopic examination was over 95%, to ensure that most of them were single cells, and then used for mutagenesis treatment.

[0052] ARTP mutagenesis treatment: adjust the plasma generating gas-helium flow rate to 12.5L / min; the distance between the p...

Embodiment 2

[0058] Morphological and culture characteristics of embodiment 2 bacterial strain HS807-AN-2396 (CGMCC No.10576)

[0059] The experiments were carried out with reference to the relevant contents in the "Streptomyces Identification Manual", "Classification and Identification of Actinomycetes", "Common Bacterial System Identification Manual" and "Molecular Cloning Experiment Guide".

[0060] Relevant symbols indicate explanation: 0: no growth; 1: weak growth; 2: able to grow, with a few spores; 3: good growth, with a large number of spores; 4: best growth, with abundant spores; +: positive; -: Negative.

[0061] Culture characteristics: Nine mediums of ISP1, ISP2, ISP3, ISP4, ISP5, Gaoshi No. 1, calcium malate, YMS and Cha's (obtained from Zhejiang Hisun Pharmaceutical Co., Ltd.) were used, and cultured at 28°C for 6~ After 8 days, observe the color and pigment situation of mycelia.

[0062] Table 1 Culture characteristics of bacterial strain HS807-AN-2396 on 9 kinds of media ...

Embodiment 3

[0065] Physiological and biochemical characteristics of Example 3 bacterial strain HS807-AN-2396 (CGMCC No.10576)

[0066] The culture conditions were all cultured at 28°C for 6-8 days.

[0067] a) Carbon source: ISP9 was used as the basal medium, and the final concentrations of various carbon sources were all 1.0%, and the stated percentages were mass percentages.

[0068] b) Inorganic nitrogen source: ISP9 was used as the basic medium, and the concentrations of potassium nitrate and ammonium sulfate were both 0.1%.

[0069] The utilization of carbon source and inorganic nitrogen source is shown in Table 2. The results of Table 2 show that strain HS807-AN-2396 has different degrees of utilization of different carbon sources, and can well utilize D-glucose, maltose, and D-lactose, but D-xylose, L-arabinose and glycine are not utilized. Ammonium nitrogen sources can be effectively utilized; however, nitrate nitrogen sources are difficult to utilize.

[0070] The utilization ...

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Abstract

The invention discloses kibdelosporangium aridum and a preparation method of an oritavancin intermediate. The kibdelosporangium aridum strain HS807-AN-2396 with high yield of the oritavancin intermediate is preserved in the China General Microbiological Culture Collection Center (CGMCC), and is assigned with the accession number of CGMCC No.10576. The preparation method of the oritavancin intermediate comprises the following step: fermenting the kibdelosporangium aridum CGMCC No.10576 in a fermentation medium, thus obtaining the oritavancin intermediate A82846B from the fermentation broth. With the adoption of the preparation method, the high yield, namely, 2315mg / L of the fermentation potency of the oritavancin intermediate can be realized on a 60m<3> tank, and thus the industrial production of oritavancin is facilitated.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a method for preparing an intermediate of Cystoids desertum and oritavancin. Background technique [0002] Aerobic Gram-positive cocci are important pathogens of bacterial infections. Since the late 1980s, the infections caused by such bacteria have been on the rise. However, the increasing drug resistance of Gram-positive cocci has brought serious challenges to the treatment of infectious diseases. Teicoplanin and vancomycin are currently commonly used glycopeptide drugs for the treatment of drug-resistant Gram-positive bacterial infections. However, with the increasingly widespread clinical application, vancomycin-resistant Staphylococcus aureus (VISA, VRSA) and vancomycin-resistant Enterococcus (VRE) have also appeared in various parts of the world. Therefore, teicoplanin and vancomycin cannot fully meet the clinical needs, and it is necessary to develop and apply new gly...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N1/14C12P21/02C12R1/645
Inventor 郑玲辉洪云邱海潇徐长安陈峰熊正军白骅
Owner ZHEJIANG HISUN PHARMA CO LTD
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