CN102234675B - Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation - Google Patents
Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation Download PDFInfo
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Abstract
The invention provides a fermentation medium and a corresponding fermentation method in favor of efficiently producing an antibiotic A40926 with Nonomuraea.sp by fermentation. The fermentation medium comprises a carbon source and a nitrogen source, wherein, the carbon source is an organic carbon source with the content of 5-180g/L, the nitrogen source is an organic nitrogen source with the content of 2-210g/L, and the contents are measured as the total volume of the medium. By optimizing the components and ratio of carbon and nitrogen source of the fermentation medium, the cultural temperature, PH value and other fermentation parameters are optimized, so that the output of the A40926 is greatly improved. According to the method provided by the invention, the fermentation unit of the A40926 is greatly improved, so that the method is suitable for large-scale production of the A40926.
Description
Technical field
The invention belongs to industrial microbial technology field, particularly a kind of Xin Yeye village actinomycete fermentation is produced fermention medium and the corresponding fermentation process of microbiotic A40926.
Background technology
1984, scientist found microbiotic A40926 during from the Madura of soil (Actinomadura) strain bacterium in culture of isolated.And on June 8th, 1984, bacterial strain is preserved in to U.S.'s tissue culture preservation center (American Tissue Culture Collection, ATCC), numbering ATCC39727.This strain is considered to belong to streptomyces at first, after after further study, the particularly research to Cell wall synthesis, in 2003, is produced bacterium and is ranged Ye Ye village actinomyces (Nonomuraea.sp).A40926 belongs to vancomycin microbiotic, has the ability in conjunction with acyl group-D-propylamine acyl group-D-alanine.Gram-positive microorganism and neisseria gonorrhoeae (Neisseria gonorrhoeae) are had to good antibacterial effect, and there is the longer transformation period.
Dalbavancin is to take the semi-synthetic glycopeptides class microbiotic that A40926 is precursor.Dalbavancin Shi You Vicuron company development research at first, is in III clinical trial phase at present.Dalbavancin has good anti-microbial activity to gram-positive microorganism, and its mechanism of action is identical with teicoplanin with vancomycin, is mainly used in complicacy skin, soft tissue infection that treatment is caused by gram-positive microorganism.But the biological activity that it is stronger and longer transformation period make it have more tempting DEVELOPMENT PROSPECT.Along with the continuous appearance of resistant organism, and the microbiotic with good anti-MRSA and VRE effect is developed slowly.Therefore, the appearance of dalbavancin has brought new hope and breakthrough to clinical treatment resistant organism, and also attracting attention of insider extremely of the microorganism fermentation process of its precursor A40926.At present, A40926 is mainly produced by fermentation by gondola VicuronPharmaceuticals drugmaker, but the fermentating formula of its report is only some simple minimal mediums, and culture temperature is 28 ℃, incubation time 160h.Because the nutritive ingredient of its fermention medium kind is only some simple inorganic salt, thalline vigor is poor, and fermentation unit is lower, and the highest fermentation unit of its report is 128mg/L, and at present new zymotechnique both domestic and external there are no report.
Summary of the invention
Therefore, the technical problem to be solved in the present invention is exactly to produce the low deficiency of microbiotic A40926 fermentation unit for the existing Ye Ye of utilization village actinomycete fermentation, a kind of new fermention medium and corresponding fermentation process for Ye Ye village actinomycete fermentation production microbiotic A40926 are provided, it can improve the fermentation unit of A40926 greatly, enhances productivity.
The present invention solves the problems of the technologies described above one of adopted technical scheme: a kind of fermention medium for Ye Ye village actinomycetes (Nonomuraea.sp) fermentative production microbiotic A40926, comprise Carbon and nitrogen sources, wherein, described carbon source is organic carbon source, content is 5-180g/L, described nitrogenous source is organic nitrogen source, and content is 2-210g/L, and described content is by the cumulative volume of substratum.
In fermention medium of the present invention, described organic carbon source comprises various organic carbon sources conventional in substratum, preferably for being selected from one or more in glucose, maltodextrin, W-Gum and Zulkovsky starch, glucose and be selected from least one the mixture in maltodextrin, W-Gum and Zulkovsky starch more preferably.The consumption 5-180g/L of organic carbon source, preferably 15-100g/L.Wherein glucose preferably scope be 5-20g/L, maltodextrin preferably scope is 10-80g/L, W-Gum preferably scope is 10-60g/L, Zulkovsky starch preferably scope is 5-20g/L.
In fermention medium of the present invention, described organic nitrogen source comprises in substratum conventional various organic nitrogen sources, preferably for being selected from one or more in soybean cake powder, cottonseed meal, peptone and yeast extract (powder).Described soybean cake powder preferably can be selected from hot moulding soybean cake powder and/or cold press soybean cake powder.Described peptone is one or more in soy peptone, Tryptones and meat peptone preferably.Described yeast extract (powder) is to adopt fresh yeast emulsion through self-dissolving, enzymolysis, separation, refining a kind of solubility paste or the powdery natural product forming of technology such as concentrated.Described organic nitrogen source is more preferably selected from least one in soybean cake powder, cottonseed meal and peptone and is selected from yeast and soaks at least one the mixture in powder and yeast extract.The consumption of organic nitrogen source is 2-210g/L, preferably 30-50g/L.Wherein hot moulding soybean cake powder preferably scope be 5-40g/L, cold press soybean cake powder preferably scope is 5-40g/L, cottonseed meal preferably scope is 5-30g/L, soy peptone preferably scope is 2-20g/L, Tryptones preferably scope is 2-20g/L, meat peptone preferably scope is 2-20g/L, yeast soak powder preferably scope be 5-100g/L, yeast extract preferably scope is 5-100g/L.
In fermention medium of the present invention, as the actinomycetic fermention medium in conventional Ye Ye village, preferably also further comprise amino acid.One or more in the preferred α-amino-isovaleric acid of described amino acid, leucine and Isoleucine, best is α-amino-isovaleric acid.Amino acid whose consumption is 0.5-3.0g/L, and preferably scope is 1.0-2.5g/L.
In fermention medium of the present invention, preferably also further comprise metal ion.One or more in described metal ion preferably copper ion, magnesium ion and ferrous ion.The consumption of metal ion is 0.05ppm-12.0ppm, and preferably scope is 0.5-10.0ppm.
In fermention medium of the present invention, as the actinomycetic fermention medium in conventional Ye Ye village, preferably also further contain mineral substance.Described mineral substance is generally as osmotic pressure regulator, and its consumption is 1.0-5.0g/L preferably.Described mineral salt can be the various mineral salts that use in conventional fermention medium, preferably NaCl.
Fermention medium of the present invention, as the fermention medium of conventional antibiosis streptomycete, preferably can also contain defoamer.The consumption of defoamer is conventional amount used.
A preferred embodiment of the present invention is that fermention medium of the present invention comprises:
5-20g/L glucose;
At least one in 5-80g/L maltodextrin, W-Gum and Zulkovsky starch;
At least one in 2-40g/L soybean cake powder, cottonseed meal and peptone;
At least one in 5-100g/L yeast extract and yeast extract powder; With
0.5-3.0g/L α-amino-isovaleric acid.
Another preferred embodiment of the present invention is that fermention medium of the present invention comprises: glucose 5-20g/L, dextrin 10-80g/L, W-Gum 10-60g/L, cold press soybean cake powder 5-40g/L, cottonseed meal 5-30g/L, soy peptone 2-20g/L, meat peptone 2-20g/L, yeast soak powder 5-100g/L, α-amino-isovaleric acid 0.5-3.0g/L, NaCl 1.0-5.0g/L and CuSO
40.5-10.0ppm.
The pH value of fermention medium of the present invention is pH5.0-8.5, more preferably pH5.5-8.0 preferably.
The present invention solves the problems of the technologies described above two of adopted technical scheme: the fermentation method for producing of a kind of microbiotic A40926, comprises step:
(a) seed liquor of Jiang Yeye village actinomycetes (Nonomuraea.sp) is inoculated in fermention medium and carries out liquid fermentation and culture, and described fermention medium is any one fermention medium as above;
(b) from fermented liquid, isolate microbiotic A40926.
In step (a), the actinomycetic seed liquor in described Ye Ye village is cultivated and is obtained by method Jiang Yeye village actinomycetes routinely in seed culture medium.Described seed culture medium can be the actinomycetic seed culture medium in existing Ye Ye village, better ISP2 substratum and the M707 substratum of being selected from.The temperature of seed culture is 25-32 ℃ preferably.
In the present invention, described Ye Ye village actinomycetes can be existing various antibiosis streptomycete bacterial strain, preferably Ye Ye village actinomycetes ATCC39727.
In step (a), the temperature of described fermentation culture is 20-40 ℃, is preferably 25-37 ℃; Preferred pH is 5.0-8.5, and preferably scope is 5.5-8.0.
In step (b), the method for isolating microbiotic A40926 from fermented liquid can be conventional method, is generally that fermented liquid is adjusted to alkalescence, and centrifuging and taking supernatant after 50 ℃ of incubations obtains microbiotic A40926 from supernatant.
In the present invention, above-mentioned optimum condition can arbitrary combination on the basis that meets this area general knowledge, obtains the preferred embodiments of the invention.
The raw material that the present invention is used or reagent except special instruction, equal commercially available obtaining.
Than prior art, beneficial effect of the present invention is as follows: the invention provides fermention medium and corresponding fermentation process that a kind of Ye Ye of being conducive to village actinomycetes high-efficiency fermenting is produced microbiotic A40926.By carbon nitrogen source composition and the proportioning of preferred fermention medium, optimize the fermentation parameters such as culture temperature, pH, thereby greatly improve the output of A40926.The fermentation method for producing of A40926 provided by the invention has significantly improved the fermentation unit of A40926, is applicable to the large-scale production of A40926.
Embodiment
With embodiment, further illustrate the present invention below, but the present invention is not limited.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, or the condition of advising according to manufacturer.
Embodiment 1
Get Yi Zhuyeye village actinomycetes (Nonomuraea.sp) ATCC39727 and line seed slant medium, after 30 ℃ of cultivation 7d, be inoculated in shake-flask seed substratum, liquid amount is 20ml/250ml, and in 30 ℃, the rotary shaking table of 200rpm is cultivated 72h.Seed liquor be take 10% (v/v) inoculum size and is inoculated in the 250ml fermentation shake flask that liquid amount is 20ml and ferments, 30 ℃ of leavening temperatures, fermentation period 5d.After fermentation ends, fermented liquid is adjusted to pH to 12.0 with NaOH, centrifuging and taking supernatant after 50 ℃ of incubation 1h, HPLC measures, and A40926 output reaches 366mg/L.
Wherein slant medium used forms: ISP2 substratum, and component is glucose 4.0g/L, and yeast soaks powder 4.0g/L, and Fructus Hordei Germinatus soaks powder 10.0g/L, agar powder 20g/L, pH7.3.
Seed culture medium used forms: ISP2 substratum, and component is glucose 4.0g/L, and yeast soaks powder 4.0g/L, and Fructus Hordei Germinatus soaks powder 10.0g/L, pH7.3.
The composition of fermention medium: glucose 5.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH8.0.
Embodiment 2
Fermention medium forms: glucose 10.0g/L, and dextrin 5.0g/L, yeast soaks powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.A40926 output reaches 98mg/L.
Embodiment 3
Fermention medium forms: glucose 10.0g/L, and dextrin 5.0g/L, yeast soaks powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 180mg/L.
Embodiment 4
Fermention medium forms: glucose 10.0g/L, and dextrin 50.0g/L, yeast soaks powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 175mg/L.
Embodiment 5
Fermention medium forms: glucose 10.0g/L, and dextrin 30.0g/L, Zulkovsky starch 10.0g/L, yeast soaks powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 210mg/L.
Embodiment 6
Fermention medium forms: glucose 5.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, yeast soaks powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 214mg/L.
Embodiment 7
Fermention medium forms: glucose 5.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, yeast soaks powder 10.0g/L, cold press soybean cake powder 20.0g/L, soya peptone 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 226mg/L.
Embodiment 8
Fermention medium forms: glucose 5.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, yeast extract 10.0g/L, cold press soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 218mg/L.
Embodiment 9
Fermention medium forms: glucose 10.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, yeast soaks powder 10.0g/L, cold press soybean cake powder 20.0g/L, soy peptone 10.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 234mg/L.
Embodiment 10
Fermention medium forms: glucose 10.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, meat peptone 10.0g/L, yeast soaks powder 10.0g/L, cold press soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 256mg/L.
Embodiment 11
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 10.0g/L, cold press soybean cake powder 20.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 292mg/L.
Embodiment 12
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 20.0g/L, cottonseed meal 10.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 308mg/L.
Embodiment 13
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 10.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 320mg/L.
Embodiment 14
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 325mg/L.
Embodiment 15
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 334mg/L.
Embodiment 16
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 7.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 304mg/L.
Embodiment 17
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 28 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 298mg/L.
Embodiment 18
Fermention medium forms: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soaks powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, α-amino-isovaleric acid 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 5d, other conditions are with embodiment 1.The output of A40926 reaches 366mg/L.
Embodiment 19
Fermention medium forms: glucose 10g/L, W-Gum 10g/L, cold press soybean cake powder 5g/L, meat peptone 2g/L, α-amino-isovaleric acid 3g/L, CuSO
40.5ppm, pH to 5.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 20 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 234mg/L.
Embodiment 20
Fermention medium forms: glucose 10g/L, Zulkovsky starch 20g/L, soy peptone 2g/L, α-amino-isovaleric acid 0.5g/L, CuSO
410ppm, pH to 8.5.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 40 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 197mg/L.
Embodiment 21
Fermention medium forms: dextrin 10g/L, and Zulkovsky starch 5g/L, cold press soybean cake powder 40g/L, Tryptones 2g/L, yeast soaks powder 50g/L, α-amino-isovaleric acid 1g/L, NaCl 1g/L, pH to 7.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 37 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 175mg/L.
Embodiment 22
Fermention medium forms: glucose 5g/L, hot moulding soybean cake powder 5g/L, Tryptones 20g/L, α-amino-isovaleric acid 1g/L, NaCl 5g/L, pH to 7.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 37 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 190mg/L.
Embodiment 23
Fermention medium forms: glucose 20g/L, and dextrin 80g/L, W-Gum 60g/L, hot moulding soybean cake powder 40g/L, cottonseed meal 30g/L, soy peptone 20g/L, meat peptone 20g/L, yeast soaks powder 100g/L, α-amino-isovaleric acid 1g/L, NaCl 2g/L, pH to 8.0.
By 1 seed making in embodiment, with 10% (v/v) inoculum size, be inoculated in fermention medium, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 289mg/L.
Comparative example 1
Press document " Zuzana TD, Fabrizio D, Salvatore M, et al.Design of mineralmedium for growth of Actinomadura sp.ATCC39727, producer of theglycopeptide A40926:effects of calcium ions and nitrogen sources[J] .ApplMicrobiol Biotechnol, 2004, 65:671-677. " described method, by take inoculum size 10% (v/v) by 1 seed liquor making in embodiment, be inoculated in the 250ml fermentation shake flask that liquid amount is 20ml and ferment, 30 ℃ of temperature, fermentation period 5d.Fermentation ends secondary fermentation liquid is adjusted pH to 12.0 with NaOH, centrifuging and taking supernatant after 50 ℃ of incubation 1h, and HPLC measures, and the output of A40926 is 92mg/L.Wherein fermention medium is MM-103/Gln:L-Gln 2.0g/L, K
2hPO
40.5g/L, MgSO
40.2g/L, FeSO
40.01g/L, glucose 10.0g/L, pH7.0-7.2.
Claims (5)
1. the fermention medium for Ye Ye village actinomycetes (Nonomuraea.sp) fermentative production microbiotic A40926, comprise Carbon and nitrogen sources, it is characterized in that, described carbon source is organic carbon source, content is 5-180g/L, described nitrogenous source is organic nitrogen source, and content is 2-210g/L, and described content is by the cumulative volume of substratum; Actinomycetes Shi Yeye village, described Ye Ye village actinomycetes ATCC39727;
Described fermention medium comprises:
Glucose 5-20g/L, dextrin 10-80g/L, W-Gum 10-60g/L, cold press soybean cake powder 5-40g/L, cottonseed meal 5-30g/L, soy peptone 2-20g/L, meat peptone 2-20g/L, yeast soak powder 5-100g/L, α-amino-isovaleric acid 0.5-3.0g/L, NaCl1.0-5.0g/L and CuSO
40.5-10.0ppm.
2. a fermentation method for producing of microbiotic A40926, is characterized in that, comprises step:
(a) seed liquor of Jiang Yeye village actinomycetes (Nonomuraea.sp) is inoculated in fermention medium and carries out liquid fermentation and culture, and described fermention medium is fermention medium as claimed in claim 1;
(b) from fermented liquid, isolate microbiotic A40926.
3. method as claimed in claim 2, is characterized in that, in step (a), and actinomycetes Shi Yeye village, described Ye Ye village actinomycetes ATCC39727.
4. method as claimed in claim 2, is characterized in that, in step (a), the temperature of described fermentation culture is 20-40 ℃.
5. method as claimed in claim 2, is characterized in that, in step (a), the pH of described fermentation culture is 5.0-8.5.
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| CN105671110B (en) * | 2015-05-05 | 2019-02-01 | 重庆乾泰生物医药有限公司 | A method of producing Dalbavancin precursor A40926 |
| CN110105435B (en) * | 2019-05-08 | 2023-12-08 | 宜昌东阳光生化制药有限公司 | Fermentation medium and fermentation method for producing A40926 |
| CN110551786B (en) * | 2019-09-12 | 2021-12-07 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| CN112625925B (en) * | 2021-01-08 | 2022-04-19 | 浙江大学 | High-yield strain of dalbavancin precursor A40926B0 and application thereof |
| CN113980860B (en) * | 2021-11-23 | 2023-09-08 | 天津商业大学 | Nonomuria with high yield of prastatin and 2 '-amino-2' -deoxyadenosine and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1732263A (en) * | 2002-10-23 | 2006-02-08 | 维柯龙药品公司 | Genes and proteins for the biosynthesis of the glycopeptide antibiotic A40926 |
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| JP2011116662A (en) * | 2008-03-26 | 2011-06-16 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | New antibiotic sf2876 substance, method for producing the same, and pharmaceutical composition |
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| CN1732263A (en) * | 2002-10-23 | 2006-02-08 | 维柯龙药品公司 | Genes and proteins for the biosynthesis of the glycopeptide antibiotic A40926 |
Non-Patent Citations (1)
| Title |
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| 沈晓放等.A40926产生菌的培养基优化及菌种选育.《第十一届全国抗生素（微生物药物）学术会议论文集》.2009,98-102. * |
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