阅读说明：本技术 一种泰乐菌素混种发酵方法 (Mixed fermentation method of tylosin ) 是由 郭佳 王少云 刘晓明 石雷 李芳� 于 2020-06-30 设计创作，主要内容包括：本发明涉及一种泰乐菌素混种发酵方法,该方法是在以弗式链霉菌为发酵菌种,在生产泰乐菌素的发酵过程中接入培养好的芽孢状态的双球菌继续发酵。本发明利用双球菌与弗式链霉菌混合发酵生产泰乐菌素,其中双球菌和弗式链霉菌在发酵体系中混合培养,共用其代谢酶系和代谢中间体,对泰乐菌素的合成有明显的促进作用,从而有效提高了发酵水平,改善了发酵液的组分含量,尤其是泰乐菌素A的含量。通过本发明的方法,可使泰乐菌素的发酵周期控制在160～170小时,发酵单位较原工艺提高10%以上,发酵液中泰乐菌素A效价提高10%以上,对发酵液过滤无影响。(The invention relates to a tylosin mixed culture fermentation method, which is characterized in that streptomyces fradiae is used as a fermentation strain, and a cultured spore-state diplococcus is inoculated in the fermentation process for producing tylosin for continuous fermentation. The method utilizes the mixed fermentation of the diplococcus and the streptomyces fradiae to produce the tylosin, wherein the diplococcus and the streptomyces fradiae are mixed and cultured in a fermentation system, and share a metabolic enzyme system and a metabolic intermediate thereof, so that the method has obvious promotion effect on the synthesis of the tylosin, thereby effectively improving the fermentation level and improving the component content of the fermentation liquor, particularly the content of the tylosin A. By the method, the fermentation period of the tylosin can be controlled within 160-170 hours, the fermentation unit is improved by more than 10% compared with the original process, the titer of the tylosin A in the fermentation liquor is improved by more than 10%, and the tylosin A has no influence on the filtration of the fermentation liquor.)

1. A tylosin mixed culture fermentation method is characterized in that: in the fermentation culture process of producing tylosin by taking streptomyces fradiae as a fermentation strain, the cultured gemma diplococcus is inoculated and then fermentation is continued.

2. The fermentation method of the tylosin mixture according to claim 1, wherein: the diplococcus is inoculated in fermentation culture for 90-100 hours.

3. The mixed tylosin fermentation process according to claim 1 or 2, wherein the inoculum size of the diplococcus is 0.05-0.1%.

4. The fermentation method of mixed tylosin according to claim 3, wherein said diplococcus sporogenes is prepared by: inoculating the diplococcus liquid into a sterilized shake flask culture medium, culturing for 10-14 hours at the temperature of 29-33 ℃ in a shaking table at 170-220 revolutions, and performing microscopic examination on the bacteria to form spores;

the shake flask culture medium consists of: 2.0-3.0% of glucose, and corn steep liquor: 0.1-0.2% of yeast extract, 0.2-0.3% of calcium carbonate and a proper amount of soybean oil.

Technical Field

The invention relates to biological and new medical technology, in particular to a tylosin mixed culture fermentation method.

Background

Tylosin (Tylosin), also known as Tylosin, is a macrolide antibiotic with broad antimicrobial spectrum, strongest antimicrobial activity against mycoplasma, low toxicity and broad spectrum, and can be used for treating infections caused by penicillin-resistant bacteria, mainly against G⁺For most part G^-Spirochetes and large viruses also play a role. Tylosin is mainly composed of four components of tylosin A, B, C, D. A, B, C has antibacterial activity except tylosin D component, wherein the antibacterial activity of A component is the highest. Among tylosin currently produced, the a component is the main component of tylosin.

Disclosure of Invention

The invention aims to provide a tylosin mixed strain fermentation method which can effectively improve the content of a tylosin A component in tylosin fermentation and improve the fermentation level.

The technical scheme adopted for realizing the aim of the invention is as follows:

a tylosin mixed culture fermentation method is characterized in that: in the fermentation culture process of producing tylosin by taking streptomyces fradiae as a fermentation strain, the cultured gemma diplococcus is inoculated and then fermentation is continued.

The diplococcus is inoculated in fermentation culture for 90-100 hours.

The inoculation amount of the diplococcus is 0.05-0.1%.

The preparation method of the gemma diplococcus comprises the following steps: inoculating the diplococcus liquid into a sterilized shake flask culture medium, culturing for 10-14 hours at the temperature of 29-33 ℃ in a shaking table at 170-220 revolutions, and performing microscopic examination on the bacteria to form spores;

the shake flask culture medium consists of: 2.0-3.0% of glucose, and corn steep liquor: 0.1-0.2% of yeast extract, 0.2-0.3% of calcium carbonate and a proper amount of soybean oil.

The control of the fermentation process is based on the prior disclosed tylosin fermentation production process, such as the tylosin production process published in the journal of industrial technology.

The method utilizes the mixed fermentation of the diplococcus and the streptomyces fradiae to produce the tylosin, wherein the diplococcus and the streptomyces fradiae are mixed and cultured in a fermentation system, and share a metabolic enzyme system and a metabolic intermediate thereof, so that the method has obvious promotion effect on the synthesis of the tylosin, thereby effectively improving the fermentation level and improving the component content of the fermentation liquor, particularly the content of the tylosin A. By the method, the fermentation period of the tylosin can be controlled at 160-170 hours, the fermentation unit is improved by more than 10% compared with the original process, the titer of the tylosin A in the fermentation broth is improved by more than 10%, and the fermentation broth is not influenced.

Detailed Description

The invention is illustrated below by way of examples, which are to be understood as being illustrative and not limiting. The scope and core content of the invention are to be determined by the claims.

The following examples diplococcal medium consists of: 2.0-3.0% of glucose, and corn steep liquor: 0.1-0.2% of yeast extract, 0.2-0.3% of calcium carbonate and a proper amount of soybean oil.