Producing strain of oritavancin intermediate and application of producing strain

Abstract

The invention discloses a producing strain of an oritavancin intermediate (A82846B) and application of the producing strain. The producing strain kibdelosporangium aridum JH100-32B16B of the oritavancin intermediate is preserved in China General Microbiological Culture Collection Center (CGMCC), and the preservation number is CGMCC No.17931. The fermentation method is a method for producing the oritavancin intermediate by fermenting the kibdelosporangium aridum CGMCC No.17931 in a fermentation culture medium. By adopting the producing strain and a corresponding fermentation process thereof, the fermentation titer of A82846B can be 1450mg / L on a 30L fermentation tank by adopting a fermentation culture medium with a low-cost formula, and the fermentation cost is reduced by more than 90% compared with that of a contrast process; and the "impurity-product ratio" (A / B ratio) is as low as 1.5-2.0, and is reduced by more than half compared with a control level, thereby being beneficial to simplifying a product extraction process and reducing the extraction cost. The advantages in two aspects are combined, so that the comprehensive production cost of the A82846B is obviously lower than a control process level reported in the existing literature.

Description

technical field [0001] The present invention relates to a production bacteria selection and fermentation technology of a pharmaceutical intermediate, in particular to a microbial strain breeding for producing oritavancin intermediate A82846B component and a corresponding fermentation process. Background technique [0002] At present, in the field of antibacterial infection drugs, β-lactam broad-spectrum antibiotics represented by penicillins and cephalosporin antibiotics are widely used in clinical practice. Due to long-term and high-dose inappropriate use, a large number of drug-resistant pathogenic bacteria have emerged in recent years and have continued to evolve, making traditional first-line antibiotics encounter the dilemma of poor or even ineffective antibacterial effects. [0003] Glycopeptide antibiotics have a good antibacterial effect on common drug-resistant bacteria with β-lactamase due to their different mechanisms of action from β-lactam antibiotics. As a rep...

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Problems solved by technology

However, the fermentation process reported in this patent and subsequent documents has the following three defects: the one is that the target component A82846B fermentation titer is low (150mg / L); Expensive raw materials lead to high fermentation costs; the third is that the fermentation broth contains three homologues: A82846A, A82846B, and A82846C (respectively referred to as "A component", "B component", and "C component"), of which , the proportion of A component as an impurity is too high (A / B ratio is 3-4), which makes it difficult to separate the target product, and the extraction yield is low and the cost is high

But the probability of natural mutation is very low, only 10 -9 ~10 -6 , can not meet the needs of scientific research and actual production

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