CS239474B1 - Process for fermentation preparation of antibiotics - Google Patents

Abstract

A method is described for the fermentation preparation of antibiotics such as penicillin, chlortetracycline and fungicidal by culturing the relevant production microorganisms in liquid nutrient media containing assimilable monosaccharides and disaccharides as standard carbon sources, growth factors, mineral salts and finely ground psophocarp flour as the main complex nitrogen source as a substitute for the standard soybean or peanut flour used for the preparation of fermentation media, while achieving adequate production of biosynthetic substances.

Description

(54) A method of fermentation preparation of antibiotics

A method for fermenting the preparation of antibiotics such as penicillin, cortlortetracycline and fungicidin by culturing the respective production microorganisms in liquid nutrient media containing assimilable monosaccharides and disaccharides as growth carbon, growth factors, mineral salts and finely ground psofocarp flour as a major nitrogen source is described. for the standard use of soy or peanut flour for the preparation of fermentation media, while achieving adequate production of biosynthetic substances ·

The method of fermentative preparation of antibiotics consists in culturing the production microorganisms in liquid nutrient media which contain assimilable carbohydrates such as glucose and other monosaccharides as carbon sources, longer disaccharides such as sucrose, lactose and the like; soybean or acarid flour are used as complex nitrogen sources, cotton flour, corn extract and other nitrogen substances * Fermentation media contain growth factors, vitamins and minerals * In the case of penicillin fermentation, glucose and lactose are mainly used as carbon sources, tetrecycline antibiotics are sucrose, molasses or enzymatic hydrolyzates of Starch; In the case of fungicidine fermentation, glucose is used as standard. Soy flour, or arachis flour and corn extract are used in the fermentation preparation of said antibiotics.

The method of fermentation preparation of some antibiotics according to the invention describes a fermentation based on psofocarp flour in an amount of 1 to 6% by weight as a substitute for soy and peanut flour, which are commonly used for the preparation of fermentation media. The amino acid composition of finely ground Fsophocarpus tetragonolobus is similar to that of soy and peanut flour.

The fermentation process for the preparation of penicillin, chlortetracycline (CTC) and fungicidin according to the invention is given by the following examples.

He did

Inoculate a 500 ml boiling flask containing Penicilllum chrysogenum CC1I F-713 containing 60 ml of a seed medium of the following composition: maize extract 22.5 g, sucrose 30 g, CaCO4 g, ammonium sulphate 5 g, water and 1000 ml; pH of the medium 5.2; cultivation is carried out on a rotary shaker at 25 ° C for 48 hours. A 500 ml boiling flask containing 40 ml of a fermentation medium of the following composition is inoculated with the grown culture in an amount of 0% by volume: corn extract 27.2 g, soya flour 16 g, lactose 110 g, potassium dihydrogen phosphate 6 g, ammonium nitrate 8 g, sodium sulphate 8 g, magnesium sulfate 1 g, sucrose 15 g, CaCO 4 10 g, phenoxyacetic acid 5.3 wt. 150 ml, water 800 ml; pH of the medium 6.2; cultivation is carried out on a rotary shaker at 25 ° C for 8 days. In the soy flour control procedure, a production of 19,600 U penicillin / ml medium is achieved; with application of 1 wt. psofocarp flour as a substitute for soya flour, penicillin production amounts to 20,000 U / ml of medium; psofocarp flour achieves a production of 20,300 U penicillin / ml medium and in a fermentation medium with 3 wt. psofocarp flour, penicillin production amounts to 19,100 U / ml medium.

Example 2

Penicilllum chrysogenum CCM F-679 strain is used to inoculate a 500 ml boiling flask containing 60 ml of inoculum medium of the following composition: glucose 30 g, lactose 10 g, corn extract 22,5 g, ammonium sulphate 2 g, CaCO4 5 g, dihydrogen phosphate potassium 0,5 g, water ed 1000 ml; pH of the medium 5.2. Cultivation is carried out at 25 ° C on a rotary shaker for 48 hours; 500 ml boiling flasks containing 40 ml of fermentation medium of the following composition: cotton flour (Pharmedia) 25 g, lactose 150 g, ammonium sulphate 10.5 g, CaCO4 10 g, sulphate calcium 5 g, ammonium sulfate 4 g, potassium dihydrogen phosphate 0.5 g, phenoxyacetic acid 5.3 wt. 150 ml, water 800 ml; pH of the medium 6.2; cultivation is carried out on a rotary shaker at 25 ° C for 10 days. In the cotton flour control procedure, a production of 28,300 U of penicillin / ml medium is achieved; replacing this substrate with 2 wt. psofocarp flour produced 21,800 U penicillin / ml medium, applied at 3 wt. psofokarp. the flour produced 25,000 U penicillin / ml medium and with 4 wt. psofokarp. flour penicillin production of 26,000 U / ml fermentation medium from the same culture time.

Example 3

Inoculate a 500 ml boiling flask containing Streptomyces aureofadens CCM 3406 containing 80 ml of inoculum medium of the following composition: sucrose 40 g, psofocarp flour 20 g, corn extract 4.8 g, ammonium sulphate 5 g, NaCl 2 g, CaCO ^ 6 g, water and 1000 ml; pH of the medium 6.4; cultivation is carried out on a rotary shaker at 28 ° C for 24 hours; a 500 ml boiling flask containing 40 ml of fermentation medium of the following composition: sucrose 60 g, psofocarp flour 30 g, corn extract 8.2 g, corn flour 5 g, ammonium sulphate 5 g, NaCl 2.4 g, CaCO 3 6 g; water to 1000 ml; pH of the medium 6.5; the fermentation is carried out on a rotary shaker at 28 ° C for 96 hours.

In the soy flour control procedure, the production of 6,240 g CTC / ml medium is achieved, in the psofocarp flour process, the CTC production is 6,000 µg / ml fermentation medium over the same culture period.

Example 4

The procedure described in Example 1, except that the fermentation medium contains psofocarp flour and, as a substitute for corn flour, the corresponding amount of rapeseed meal. In the soy flour control procedure, the production of CTC was 6,390 yug / ml fermentation broth in 96 hours of culture, in the case of the experimental procedure, the production of 660 µg CTC / ml medium was achieved in the same fermentation time.

Example 5

A 500 ml boiling flask is inoculated with the production strain Streptomyces noursei and contains 60 ml of inoculum medium of the following composition: soya flour 10 g, glucose 30 g, ammonium sulphate 2 g, corn extract 1 g, NaCl 1 g, water and 1000 ml; pH of the medium 6.2; cultivation is carried out on a rotary shaker at 28 ° C for 24 hours; 500 ml of flasks containing 60 ml of fermentation medium of the following composition: soya flour 20 g, glucose 50 g, ammonium sulphate 3 g, corn extract 2 g, CaCO4 20 g, water to 1000 ml; pH of the medium 6.8 to 7.2. Cultivation is carried out on a rotary shaker at 28 ° C for 168 hours. In the soy flour control procedure, 59 300 µl fungicidin / ml medium is produced; when soy flour is replaced with psofocarp flour, the production of fungicidine is 58,000 U / ml of medium in the same fermentation time.

Claims (1)

DETAILED DESCRIPTION OF THE INVENTION A process for the fermentative preparation of antibiotics and other biosynthetic substances by culturing production microorganisms in a liquid nutrient medium containing assimilable carbon and nitrogen sources, mineral nutrient salts, growth agents, or biofactors under aerobic conditions, characterized in that the liquid nutrient medium contains the main complex source % of assimilable nitrogen of flour from Psophocarpus tetragonolobus in an amount of 1 to 6 wt.