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Streptomyces clavuligerus for high-yield clavulanic acid and application of streptomyces clavuligerus

A technology of Streptomyces clavulanicus and clavulanic acid, applied in the field of microorganisms, can solve the problems of unsatisfactory industrial fermentation, inability to surpass, and low clavulanic acid production

Inactive Publication Date: 2015-04-08
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The clavulanic acid production of wild-type Streptomyces clavulus is very low, which is far from meeting the needs of industrial fermentation. Therefore, the strains currently used in industry are often mutagenic strains obtained through multiple rounds of physical and chemical mutagenesis screening.
With the deepening of basic research on the biosynthesis of clavulanic acid, a variety of rational metabolic engineering methods have successfully increased the production of clavulanic acid in wild strains, but they still cannot surpass the mutagenic strains widely used in industry

Method used

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  • Streptomyces clavuligerus for high-yield clavulanic acid and application of streptomyces clavuligerus

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Effect test

Embodiment 1

[0039] Example 1. Acquisition and identification of Streptomyces clavuligerus 16CF10

[0040] 1. Acquisition of Streptomyces clavuligerus 16CF10

[0041] Using the constitutively expressed erythromycin promoter (ermE*p), the target genes glpF1 and ceas2 were overexpressed in the industrial strain Streptomyces clavuligerus 70116 through the integrated vector, respectively, and their effect on the production of clavulanate was investigated. influences. The results show that the individual overexpression of these target genes is beneficial to the improvement of clavulanic acid production in industrial strains.

[0042] Next, the inventors of the present invention constructed a reporter plasmid for simultaneously monitoring the expression of dual targets, combined the target genes glpF1 and ceas2 in pairs, and then constructed the vector and introduced it into the industrial strain Streptomyces clavuligerus 70116. Then, the mutant strains with high expression of the reporter gen...

Embodiment 2

[0053] Example 2. Production of clavulanic acid by fermenting Streptomyces clavuligerus 16CF10 CGMCC No.7915

[0054] Solid YD medium: the solvent is water, the solute and its concentration are as follows: yeast extract (product of Difco company) 4.0g / L; maltose extract (product of OXID company) 10g / L; glucose 4.0g / L; MgCl 2 2.0g / L; CaCl 2 1.5g / L; Agar 2.0g / L; pH 7.5.

[0055] Seed medium (same as fermentation medium): soybean powder 20g / L; dextrin (product of Sinopharm Chemical Reagent Co., Ltd., whose product catalog number is 69009992) 10g / L; glycerol 15mL / L; KH 2 PO 4 0.6g / L; 3-(N-morpholine)propanesulfonic acid (MOPS) 8.0g / L; trace elements 1mL / L; pH 7.0±0.2. Each concentration is the final concentration of the corresponding component in the medium. Among them, the trace element formula is as follows (100ml): FeSO 4 ·7H 2 O 100mg; MnCl 2 ·4H 2 O 100mg; ZnSO 4 ·7H 2 O 100mg; CaCl 2 ·3H 2 O 130 mg; balance is water.

[0056] 1. Production of clavulanic acid ...

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Abstract

The invention discloses a streptomyces clavuligerus for high-yield clavulanic acid, and application of the streptomyces clavuligerus. The streptomyces clavuligerus for high-yield clavulanic acid is specifically a streptomyces clavuligerus 16CF10 of which the preservation number is CGMCC No.7915 in the China General Microbiological Culture Collection Center. According to the invention, a streptomyces clavuligerus 70116 is taken as a starting strain, is subjected to metabolic engineering modification and is mutated to obtain the streptomyces clavuligerus 16CF10 CGMCC No.7915. Experimental results show that the amount of clavulanic acid produced by the strain cultivated through fermentation reaches 2.25 g / L of fermentation liquor, and is improved by about 51% compared with that the streptomyces clavuligerus 70116 serving as the starting strain, so that the streptomyces clavuligerus 16CF10 CGMCC No.7915 has a broad industrial application prospect.

Description

technical field [0001] The invention belongs to the field of microorganisms, and relates to a high-yielding clavulanic acid strain of Streptomyces coryneformis and its application. Background technique [0002] With the extensive use of antibiotics, the problem of drug resistance of pathogenic bacteria is becoming more and more serious. The abuse of β-lactam antibiotics such as penicillin and cephalosporin leads to the production of β-lactamase by some pathogenic bacteria, thereby degrading these antibiotics and producing drug resistance. Clavulanic acid, also known as clavulanic acid, is a secondary metabolite produced by Streptomyces clavuligerus. The antibacterial activity of clavulanic acid alone is very weak, but it has a unique 3R, 5R stereo conformation, which makes it have a spectral and irreversible β-lactamase inhibitory activity. It is also the first to be discovered and successfully used in clinical practice. β-lactamase inhibitors. In clinical application, cl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N1/20C12P17/18C12R1/465
Inventor 杨克迁赵友宝向四海
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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