CN101265492A - Method for increasing lincomycin yield - Google Patents
Method for increasing lincomycin yield Download PDFInfo
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- CN101265492A CN101265492A CNA2008100370802A CN200810037080A CN101265492A CN 101265492 A CN101265492 A CN 101265492A CN A2008100370802 A CNA2008100370802 A CN A2008100370802A CN 200810037080 A CN200810037080 A CN 200810037080A CN 101265492 A CN101265492 A CN 101265492A
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- lincomycin
- proline
- pro
- ala
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Abstract
The invention provides a method of increasing lincomycin production, and the method is realized through adding proline and /or lactamine into a ferment culture medium of the lincomycin. By using the method provided by the method, the proline and /or the lactamine which are not used for precursor substance in the lincomycin synthesis are added into the ferment culture medium, yield of the lincomycin can be obviously increased.
Description
Technical field
The invention belongs to biological technical field, specifically, relate to a kind of method that improves lincomycin yield.
Background technology
Lincomycin (Lincomycin, abbreviation LCM) claims U-10149 again, gram-positive microorganism there is good effect, it does not have the toxicity of cross resistance and itself lower, so be widely used in the disease that causes by gram-positive microorganism, simultaneously, Gram-negative bacteria also there is certain restraining effect.The semi-synthetic product in lincomycin and downstream thereof is called lincosamides, and lincosamides has become one of microbiotic main in the clinical application.
General said lincomycin is meant its A component, it is the microbiotic that is formed by connecting by peptide bond by hygrine PHA (trans-the N-methyl-4-n-propyl proline(Pro) (PPL)) and first sulphur lincosamide MTL (6-amino-6,8-dideoxy-1-sulfo--0-Erythro-2,3-octadecane-diol-D-semi-lactosi pyranoside) two portions.As shown in Figure 1, the biosynthetic pathway of lincomycin A is divided into two branches, two branches generate propyl group proline(Pro) (PPL) respectively but and first sulphur woods amine (MTL), wherein, the route of synthesis of propyl group proline(Pro) is as shown in Figure 2.
Foreign study is found, directly add propyl group proline(Pro) as precursor in the fermenting process and can improve the output of lincomycin A and the output of corresponding minimizing lincomycin B, relevant report is not then arranged as yet but add the output whether other non-precursor amino acid can improve lincomycin A.
Summary of the invention
The present inventor finds in the process of research raising lincomycin yield, adds proline(Pro) and/or L-Ala in the fermention medium of lincomycin, all can improve the output of lincomycin.
Therefore, the objective of the invention is to, a kind of method that improves lincomycin yield is provided, this method realizes by adding proline(Pro) and/or L-Ala in the fermention medium of lincomycin.
According to a preferred embodiment of the present invention, the suitableeest addition of proline(Pro) and L-Ala, the suitableeest interpolation time are respectively: 60-84h adds the 0.005-0.01% proline(Pro); 0-12h adds the 0.005-0.01% L-Ala.
Use method provided by the invention, by in fermention medium, be added on lincomycin synthetic in not as the proline(Pro) and/or the L-Ala of precursor substance, all can obviously improve the output of lincomycin.
Description of drawings
Fig. 1 is the biosynthetic pathway of lincomycin A.
Fig. 2 is the biosynthetic pathway of propyl group proline(Pro).
Embodiment
Below in conjunction with specific embodiment, the invention will be further described.Should be understood that following examples only are used to the present invention is described but not are used to limit scope of the present invention.
The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, the condition that conditioned disjunction production firm described in " molecular cloning: laboratory manual " (New York:Cold Spring Harbor Laboratory Press, 1989) is recommended is carried out.
In following embodiment of the present invention, the streptomyces lincolnensis (Streptomyces lincolnensis) that uses was submitted Chinese typical culture collection center (CCTCC) preservation that is positioned at Wuhan University on 04 25th, 2008, and preserving number is CCTCC M 208064.
Except that specifying, employed % in following examples, ‰ is weight ratio.
In an embodiment of the present invention, the prescription of fermention medium is: 0.8% (NH
4)
2SO
4, 0.8%NaNO
3, 0.5%NaCl, 0.02%K
2HPO
4, 3% soybean cake powder, 0.2% corn steep liquor, 0.8%CaCO
3, 5% glucose, pH7.0.
In an embodiment of the present invention, tiring of lincomycin adopts cylinder plate method to detect Chinese Pharmacopoeia 2005 editions (two ones).
1.1, the addition of proline(Pro) is to the biosynthetic influence of lincomycin
The fermention medium of preparation lincomycin, in substratum, add weight ratio respectively and be 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.2% proline(Pro), simultaneously in contrast with the substratum that do not add proline(Pro), insert streptomyces lincolnensis (Streptomyces lincolnensis) fermentation culture after 168 hours, tiring of sampling and measuring lincomycin, the result is as shown in table 1.
The addition of table 1, proline(Pro) is to the biosynthetic influence of lincomycin
| Proline(Pro) addition (%) | 0 | 0.001 | 0.005 | 0.01 | 0.05 | 0.1 | 0.2 |
| Relative potency | 100 | 103 | 114 | 110 | 107 | 105 | 102 |
By the result of table 1 as seen, add the biosynthesizing that proline(Pro) can obviously improve lincomycin in fermention medium, preferred addition scope is 0.005-0.01%.
1.2, interpolation time of proline(Pro) is to the biosynthetic influence of lincomycin
The fermention medium of preparation lincomycin, insert streptomyces lincolnensis (Streptomyces lincolnensis) fermentation culture, in substratum, added weight ratio respectively at 0,12,36,60,84,108,132 hour and be 0.005% proline(Pro), simultaneously in contrast with the substratum that do not add proline(Pro), ferment after 168 hours, tiring of sampling and measuring lincomycin, the result is as shown in table 2.
The interpolation time of table 2, proline(Pro) is to the biosynthetic influence of lincomycin
| Proline(Pro) adds the time (hr) | 0 | 12 | 36 | 60 | 84 | 108 | 132 | Contrast |
| Relative potency | 112 | 106 | 104 | 123 | 116 | 94 | 109 | 100 |
By the result of table 2 as seen, added the biosynthesizing that proline(Pro) can obviously improve lincomycin in 60 hours in fermention medium in fermentation, preferably the interpolation time is 60-84 hour.
Embodiment 2, interpolation L-Ala are to the biosynthetic influence of lincomycin
2.1, the addition of L-Ala is to the biosynthetic influence of lincomycin
The fermention medium of preparation lincomycin, in substratum, add weight ratio respectively and be 0.005%, 0.01%, 0.03%, 0.05%, 0.1% L-Ala, simultaneously in contrast with the substratum that do not add L-Ala, insert streptomyces lincolnensis (Streptomyces lincolnensis) fermentation culture after 168 hours, tiring of sampling and measuring lincomycin, the result is as shown in table 3.
The addition of table 3, L-Ala is to the biosynthetic influence of lincomycin
| L-Ala addition (%) | 0.005 | 0.01 | 0.03 | 0.05 | 0.1 | Contrast |
| Relative potency | 106 | 111 | 99 | 72 | 19 | 100 |
By the result of table 3 as seen, add the biosynthesizing that L-Ala can obviously improve lincomycin in fermention medium, preferred addition scope is 0.005-0.01%.
2.2, interpolation time of L-Ala is to the biosynthetic influence of lincomycin
The fermention medium of preparation lincomycin, insert streptomyces lincolnensis (Streptomyces lincolnensis) fermentation culture, in substratum, added weight ratio respectively at 0,12,36,60,84,108,132 hour and be 0.01% L-Ala, simultaneously in contrast with the substratum that do not add L-Ala, ferment after 168 hours, tiring of sampling and measuring lincomycin, the result is as shown in table 4.
The interpolation time of table 4, L-Ala is to the biosynthetic influence of lincomycin
| L-Ala adds the time (hr) | 0 | 12 | 36 | 60 | 84 | 108 | 132 | Contrast |
| (U/ml) tires | 113 | 105 | 88 | 101 | 91 | 89 | 94 | 100 |
By the result of table 4 as seen, added the biosynthesizing that L-Ala can obviously improve lincomycin in 0 hour in fermention medium in fermentation, preferably the interpolation time is 0-12 hour.
In sum, add proline(Pro) and L-Ala in the fermention medium of streptomyces lincolnensis (Streptomyces lincolnensis), all can obviously improve the output of lincomycin, output is the highest to have improved 23%; Its suitableeest addition, the suitableeest interpolation time are respectively: 60-84h adds the 0.005-0.01% proline(Pro); 0-12 adds the 0.005-0.01% L-Ala.
Claims (10)
1, a kind of method that improves lincomycin yield is characterized in that, this method realizes by adding proline(Pro) and/or L-Ala in the fermention medium of lincomycin.
2, the method for claim 1 is characterized in that, the prescription of the fermention medium of described lincomycin is: 0.8% (NH
4)
2SO
4, 0.8%NaNO
3, 0.5%NaCl, 0.02%K
2HPO
4, 3% soybean cake powder, 0.2% corn steep liquor, 0.8%CaCO
3, 5% glucose, pH7.0.
3, the method for claim 1 is characterized in that, the amount that described proline(Pro) adds is the 0.001-0.2% of substratum weight.
4, method as claimed in claim 3 is characterized in that, the amount that described proline(Pro) adds is the 0.005-0.01% of substratum weight.
5, the method for claim 1 is characterized in that, the time that described proline(Pro) adds is to add streptomyces lincolnensis 0-132 hour in substratum.
6, method as claimed in claim 5 is characterized in that, the time that described proline(Pro) adds is to add streptomyces lincolnensis 60-84 hour in substratum.
7, the method for claim 1 is characterized in that, the amount that described L-Ala adds is the 0.005-0.1% of substratum weight.
8, method as claimed in claim 7 is characterized in that, the amount that described L-Ala adds is the 0.005-0.01% of substratum weight.
9, the method for claim 1 is characterized in that, the time that described L-Ala adds is to add streptomyces lincolnensis 0-132 hour in substratum.
10, method as claimed in claim 9 is characterized in that, the time that described L-Ala adds is to add streptomyces lincolnensis 0-12 hour in substratum.
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|---|---|---|---|
| CN2008100370802A CN101265492B (en) | 2008-05-07 | 2008-05-07 | Method for increasing lincomycin yield |
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|---|---|---|---|
| CN2008100370802A CN101265492B (en) | 2008-05-07 | 2008-05-07 | Method for increasing lincomycin yield |
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|---|---|
| CN101265492A true CN101265492A (en) | 2008-09-17 |
| CN101265492B CN101265492B (en) | 2011-11-02 |
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|---|---|---|---|
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250991A (en) * | 2011-07-04 | 2011-11-23 | 华东理工大学 | Production method capable of improving output of lincomycin through adding glutamine |
| CN107881190A (en) * | 2017-11-15 | 2018-04-06 | 安徽大学 | The method for improving lincomycin yield by transforming Str. lincolnensis SLCG_2919 genes |
| CN109971692A (en) * | 2019-05-16 | 2019-07-05 | 华东理工大学 | Str. lincolnensis (Streptomyces lincolnensis) and cultural method and application |
| CN111117942A (en) * | 2020-01-16 | 2020-05-08 | 华东理工大学 | Genetic engineering bacterium for producing lincomycin and construction method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100572521C (en) * | 2007-05-31 | 2009-12-23 | 南阳普康药业有限公司 | Produce the production method of lincomycin with complex medium and raising output and quality |
-
2008
- 2008-05-07 CN CN2008100370802A patent/CN101265492B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250991A (en) * | 2011-07-04 | 2011-11-23 | 华东理工大学 | Production method capable of improving output of lincomycin through adding glutamine |
| CN107881190A (en) * | 2017-11-15 | 2018-04-06 | 安徽大学 | The method for improving lincomycin yield by transforming Str. lincolnensis SLCG_2919 genes |
| CN107881190B (en) * | 2017-11-15 | 2021-02-09 | 安徽大学 | Method for improving lincomycin yield by modifying streptomyces lincolnensis SLCG _2919 gene |
| CN109971692A (en) * | 2019-05-16 | 2019-07-05 | 华东理工大学 | Str. lincolnensis (Streptomyces lincolnensis) and cultural method and application |
| CN111117942A (en) * | 2020-01-16 | 2020-05-08 | 华东理工大学 | Genetic engineering bacterium for producing lincomycin and construction method and application thereof |
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| Publication number | Publication date |
|---|---|
| CN101265492B (en) | 2011-11-02 |
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