Method for enriching and extracting daptomycin from fermentation broth

Abstract

The invention relates to a method for enriching and extracting daptomycin from a fermentation broth. The method comprises the following steps: enriching the datomycin-containing fermentation broth through HZ-818 macro-porous resin, desorbing the enriched daptomycin from the macro-porous resin, performing vacuum concentration on the obtained daptomycin desorption solution, and performing precipitation crystallization by using a chemical solvent to obtain crude daptomycin; and loading the crude daptomycin into a low-pressure resin chromatography column containing a PS-RPC-300 polymer nanospherepacking material, performing chromatographic separation, performing distribution concentration to obtain a datomycin mother liquor having a purity of 97.5% or more, and performing vacuum concentration, activated carbon decolorization, precipitation crystallization and freeze drying on the mother liquor to obtain pure daptomycin having a purity of 98%. The method is simple, and the process flow issuitable for mass production.

Description

technical field [0001] The invention belongs to the technical field of industrial microorganisms, and relates to a preparation method of pharmaceutical raw materials, in particular to a preparation method of separating and purifying daptomycin from fermented mycelia. Background technique [0002] Daptomycin is the first product of a new family of antibiotics called cyclic lipopeptides. It is a cyclic lipopeptide antibiotic with a novel structure composed of thirteen amino acids extracted from the fermentation broth of Streptomyces parvus, among which ten amino acids form a ring structure, and esters are formed between decanoic acid and tryptophan outside the ring change. Not only does it have a novel chemical structure, but its mode of action is also different from any approved antibiotic. It can destroy the function of bacterial cell membrane in many ways, thereby killing Gram-positive bacteria rapidly. In addition to its ability to act on most clinically relevant Gram-p...

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Problems solved by technology

However, daptomycin is an amphoteric substance, and its isoelectric point is about PH4-5. Under different pH conditions, its solubility is different, especially daptomycin has a large number of homologues and isomers. These impurities are very similar to daptomycin in nature, therefore, it is very difficult to separate, purify or even crystallize daptomycin in industry through such a simple process

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