A kind of recombinant Streptomyces tuberculosis producing amphotericin B and its application

A technology of amphotericin and streptomyces, which is applied in the direction of bacteria, enzymes, and microorganism-based methods, can solve the problems of activity loss, etc., and achieve the effects of increasing production value, increasing the output of target products, and reducing the content of by-products
CN108441459BActive Publication Date: 2020-02-14ZHEJIANG UNIV OF TECH
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZHEJIANG UNIV OF TECH
Publication Date
2020-02-14

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Abstract

The invention discloses recombinant streptomyces nodosus capable of producing amphotericin and applications of the recombinant streptomyces nodosus. The recombinant streptomyces nodosus is obtained byimporting vitreoscilla hemoglobin (Vhb), S-adenosylmethionine synthetase (Metk), amphotericin synthetic gene cluster regulating factor (AmphRIV), secondary metabolite global regulation factor (AraC)and erythrocin strong promoter ermE*p sequences as shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 and SEQ ID NO.5 into streptomyces nodosus ZJB2016050. Through importing and overexpression of the gene, in recombinant streptomyces nodosus, the yield of amphotericin B is improved by about 45%, the yield of the by-product amphotericin A is reduced by 60%, meanwhile, the growth cycle of the thallus during the fermentation process is shortened, and thus the purpose of improving the production efficiency is achieved.
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Description

technical field

[0001] The invention relates to a method for increasing amphotericin B, reducing amphotericin A and shortening the fermentation period of strains by means of genetic engineering, in particular to a recombinant streptomyces nodosum with high amphotericin B production and application thereof. Background technique

[0002] Amphotericin B (Amphotericin B, AmB) belongs to the polyene macrolide antibiotics and has antifungal activity. In the middle of the last century, the producing bacterium, Streptomyces nodosus, was isolated and identified from soil samples in the Orinoco Delta. Recent studies have found that the fungus Penicillium nalgiovense can also produce AmB, but the yield is extremely low and has not been actually used for production. As a heptacene macrolide antibiotic, AmB has the following characteristics in its structure: it has 7 conjugated polyene macrolides, a hydroxyl group at C8, a carboxyl group at C16 and a fucosamine group at C19. AmB is mai...

Claims

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