The method of producing the antibiotic kanamycin

 

(57) Abstract:

Usage: medical industry. The inventive method of producing the antibiotic kanamycin carry out the cultivation producer Streptomyces kanamyceticus in a nutrient medium containing sources of carbon, nitrogen, phosphorus and mineral salts under conditions of aeration and mixing, while in the process of cultivation spend dolive hydrolyzed corn flour or sterile water in a quantity sufficient to maintain the viscosity at 60 100103Pas, and the first topping is produced when reaching viscosity 40103A pass.

The invention relates to the medical industry, namely the method of production of biological compounds, in particular of the antibiotic kanamycin.

The known method [1] obtain the antibiotic kanamycin by cultivation of a producer in a nutrient medium containing sources of carbon, nitrogen, phosphorus, mineral salts under conditions of aeration and mixing. Upon reaching the concentration of kanamycin in the culture fluid of 1500 µg/ml produce adding sterile water to a volume of 3 to 4 m3for 8 to 12 hours to drain.

During cultivation producer Str. kanamyceticus viscosity tion affects the mass and heat transfer between the cell and the environment. This ultimately leads to lower levels of antibioticaccutane biologically active kanamycin and increase the content in the culture fluid biologically inactive kanamycin Century To the end of fermentation to 100 hours, the concentration of kanamycin in the culture fluid is 3100 µg/ml Volume of culture fluid is 37,3 m3. Eat kanamycin in the culture fluid is 115,6 kg Solution to this problem is the improvement of mass transfer is proposed in the present method.

The aim of the invention is to increase the level of antibioticaccutane kanamycin And by reducing the content of kanamycin In the culture fluid.

The objective is achieved by the fact that in the claimed method of producing antibiotic by growing producer Str. kanamyceticus in a nutrient medium containing, by weight. corn flour 8,0 12,0; soy flour 2,0 2,5; aluminum sulfate 0,009 0,011; iron sulfate 0,005 0,007, under conditions of aeration and mixing is carried out maintaining the optimal viscosity in the range of 60 -10010-3Pass dolive sterile water or dolive hydrolyzed corn flour or a combination of both.

Example 1. Vegetative AMF inoculum culture Str. kanamyceticus grown in kolbasy 0,25; soy flour 2,0; extract of corn 0,5; chalk 0,3; potato starch 2; animal fat is 0.1. The contents of one flask is transferred in the dry inoculant capacity 2000 l containing 800 l of nutrient medium of the following composition, wt. ammonium sulfate 0.3; the fat 1,25; chalk 0,3; corn flour 3,0; soy flour 2,0; salt 0,27; the extract of corn to 0.5, and is grown at a temperature of 27 1oC for 34 40 PM Contents inoculator passed in sowing machine with a capacity of 10 m3containing 5 m3the nutrient medium of the same composition as the environment in inoculate. The duration of the growing seed -24 hours the Contents of the sowing apparatus is passed into the fermenter with a capacity of 50 m3containing 30 m3fermentation medium of the following composition, wt.

Ammonium sulfate 0,9

Animal fat 1,17

Iron sulfate 0,005

Chalk 0,5

Corn flour 8,5

Flour soy 2,0

Zinc sulfate 0.003

The extract of corn 0,3

Aminocoumarin 0,015

Propanol B-4 0,01

In the fermenter sets mode:

aeration from 0 to 44 h of growth flow increase speed from 0.25 to 1.0 volume 1 volume of medium per minute according to the following program:

Hours of growth, g air Consumption, the volume of the t 44 46 to 100 1,0

The temperature of cultivation 27 1oC, the rotational speed of the stirrer 3-1C.

Upon reaching values of viscosity of the culture fluid 40 10-3Pass to 30-40 hours to produce the first topping 2 m3sterile water. The second and third dolive carry out the viscosity, support in the range of 60 - 10010-3A pass. The time between dolive 20 24 h, the amount of topping 2 m3.

The concentration of the antibiotic kanamycin in culture liquid of 100 h is 3427 μg/ml, the amount of drain cultural liquid 39.5 m3, eat antibiotic to 136.4 kg

In a known method [1], the concentration of kanamycin in culture liquid of 100 h is 3100 µg/ml Volume of culture fluid 37,3 m3. Removal of antibiotic -115,6 kg

Example 2. The medium composition, the growing seed, the cultivation conditions are the same as in example 1.

The difference from example 1 is that when reaching a viscosity 4010-3Pass 30 40 h of growth produce first adding a hydrolysate of corn flour, the second topping produce the viscosity, keeping it in the range of 60 10010-3Pass through 20 24 hours 10 to 15 hours to drain topping produce sterile water to a volume of 2 m3according to the OEM topping hydrolyzed corn flour 3 m3.

Indicators of biosynthesis of kanamycin at 100 h are: the concentration of kanamycin in the culture fluid 3858 μg/ml, the volume of the culture fluid is drained 40 m3, eat antibiotic 154,1 kg

Operations previously known method [1] the parameters of the biosynthesis of 100 h of growth are 3100 µg/ml, the volume of 37.3 m3, eat antibiotic -115,6 kg

Literature

1. Chemistry of antibiotics. Publishing house of Academy of Sciences of the USSR, 1961, t, 1, S. 730.

The method of producing the antibiotic kanamycin by culturing producer Streptomyces kanamyceticus in a nutrient medium containing sources of carbon, nitrogen, phosphorus, mineral salts under conditions of aeration and mixing, followed by separation of the target product, characterized in that in the process of cultivation carried out dolive hydrolyzed corn flour or sterile water in a quantity sufficient to maintain the viscosity level (60 100) 10-3Pas, the first topping is produced when reaching the viscosity of the culture fluid 40 10-3PA-C.

 

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