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Method for producing daptomycin by fermentation

A technology of daptomycin and fermented liquid, which is applied in the field of fermentative production of daptomycin and antibiotics to achieve the effects of wide sources, fast utilization and low price

Active Publication Date: 2012-06-06
NEW FOUNDER HLDG DEV LLC +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] So far, there have been no reports of complex amino acids that are precursors to the daptomycin amino acid ring during feeding

Method used

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  • Method for producing daptomycin by fermentation
  • Method for producing daptomycin by fermentation
  • Method for producing daptomycin by fermentation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] 1. Preparation of amino acid solution:

[0079] Weigh amino acids with the following components and masses:

[0080] L-kynurenine: 3.67g, 3-methylglutamic acid: 2.86g, D-serine: 1.85g, D-alanine: 1.57g, L-ornithine: 2.33g, glycine: 2.65g , L-threonine: 2.10g, L-aspartic acid: 7.04g, L-asparagine: 2.33g, L-tryptophan: 3.60g; the total weight of the above amino acids is 30g.

[0081] Add the above-mentioned weighed amino acid into purified water, stir to dissolve it fully, and set the volume to 10L to obtain a compound amino acid aqueous solution with a concentration of 3.0g / L; sterilize the compound amino acid aqueous solution at 121°C for 15 minutes by high-pressure steam , cooled to obtain sterile compound amino acid aqueous solution.

[0082] 2. Fermentation and cultivation of Streptomyces roseospora NRRL11379 strain according to the following method:

[0083] The spores were inserted into 150 ml of seed medium, and the proportion of the medium was: vegetable prote...

Embodiment 2

[0090] 1. Preparation of amino acid solution:

[0091] The crude product of industrial compound amino acid contains the following amino acid composition and mass ratio:

[0092] Aspartic Acid: 7.28%, Threonine: 3.04%; Serine: 4.53%; Glutamic Acid: 8.01%; Glycine: 2.76%; Alanine: 2.54%; Cysteine: 0.79%; Valine: 2.63%; Methionine: 0.71%; Isoleucine: 1.72%; Leucine: 2.43%; Tyrosine: 0.52%; Phenylalanine: 1.35%; Lysine: 1.98%; Histidine: 1.35 %; Arginine: 5.32%; Proline: 4.01%. The total amount of amino acids is: 50.97%.

[0093] Weigh 110 g of the above-mentioned industrial compound amino acid crude product and add it into purified water, stir to make it fully dissolve, and set the volume to 10 L to obtain a compound amino acid aqueous solution with a concentration of 11.0 g / L; sterilize the compound amino acid aqueous solution at 121 ° C for 15 Minutes, cooled to obtain sterile compound amino acid aqueous solution.

[0094] 2. Fermentation and cultivation of Streptomyces ros...

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Abstract

The invention provides a method for producing daptomycin by fermentation, characterized by in the fermental cultivation process of Streptomyces roseosporus, adding an aseptic composite amino acid solution in the fermentation solution. Compared with a process without adding the composite amino acid, the method allows the fermentation unit of daptomycin to increase by more than 10 %, the impurity ingredients of products are not changed obviously, simultaneously, the method has the advantages of simple production operation, low requirement of devices, and low cost, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals and relates to a method for producing antibiotics through microbial fermentation. Specifically, the present invention relates to a method for producing daptomycin by fermentation. Background technique [0002] Daptomycin is a cyclolipopeptide antibiotic isolated from the fermentation broth of Streptomyces roseosporus, and its chemical structure is shown in formula (I). As can be seen from formula (I), daptomycin is made up of 13 amino acids and 1 long-chain fatty acid, wherein 10 amino acids form an amino acid ring, and another 3 amino acids are arranged in a line, and at the end of the L- One n-decanoic acid is linked to tryptophan (L-Trp). [0003] [0004] Formula (I) [0005] Daptomycin not only has a novel chemical structure, but its mode of action is also different from any existing antibiotics on the market: daptomycin can disrupt the translocation of amino acids by the cell membrane...

Claims

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Application Information

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IPC IPC(8): C12P21/04
Inventor 刘省伟赵德郭明刘会明别一
Owner NEW FOUNDER HLDG DEV LLC
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