Clavulanic acid is a β -lactam antibiotic. It's not a powerful antibiotic by itself, but clavulanate, potassium clavulanate, and amoxicillin potassium clavulanate is a very common antibiotic. In addition, it can be combined with ticacillin to synthesize the antibacterial drug temetine.
Source
The name comes from Streptomyces clavuligerus, a fungus that secretes clavulanic acid.
Production methods
The invention relates to a fermentation method of clavulanic acid by Streptomyces corynii, and the technological steps are as follows:
(1) Preparation of oblique strains: the lyophilized Streptomyces coryneformis strains were diluted with sterile water and then coated on the oblique surface with solid medium, the temperature was 28℃, the humidity was 40-60%, and the culture was 10-12 days. After spore production, sterile water was added to make spore suspension;
(2) Preparation of shaker seed liquid: Inoculate bevel spores into shaker seed medium at 250rpm, temperature 28℃, humidity 40-60%, and culture for 20-40 hours;
(3) Preparation of seed liquid: Inoculated the shaker seeds cultivated in step (2) into the seed tank with the inoculation amount of 0.5-2% at the temperature of 28℃, stirring speed of 300-500 RPM, gas flow rate of 0.5VM-1.0vVM, and tank pressure of 0.05-0.07MPa for 20-40 hours;
(4) Fermentation culture: Inoculated the strains cultured in step (3) into the fermenter at a inoculating rate of 5-15% (V/V), at a temperature of 28℃, stirring speed of 300-600 RPM, ventilate volume of 0.5VVM-1.2vVM, tank pressure of 0.05-0.08mpa, pH of 6.5-7.5, and supplemented with nutrients. Culture for 90-120 hours;
Wherein, the medium composition and content in step (1) are glucose 4-10g/L, malt extract 4-10g/L, yeast extract 4-10g/L, AGAR 20-25g/L, pH 6.5-7.5; The medium composition and content in the step (2) are peptone 3-10g/L, malt extract 3-10g/L, yeast extract 3-10g/L, pH 6.5-7.5; The medium composition and content in step (3) are glycerol 10-20g/L, cottonseed powder 20-30g/L, malt extract 5-15g/L, antifoaming agent 2-4g/L, pH 6.5-7.5; The medium composition and content in step (4) are glycerol 10-20g/L, cottonseed powder 40-60g/L, starch 10-20g/L, KH2PO41.0 ~ 3.5g/L, MgSO4·7H2O0.5 ~ 2.5g/L, FeSO4·7H2O0.005-0.035g/L and MnC L2 ·4H2O0.005-0.015g/L, ZnSO4·7H2O0.005-0.045g/L, antifoaming agent 2-5g/L, pH 6.5-7.5.
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