CN107365815A - A kind of fermenting and producing A40926 supplemented medium - Google Patents
A kind of fermenting and producing A40926 supplemented medium Download PDFInfo
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- CN107365815A CN107365815A CN201610318784.1A CN201610318784A CN107365815A CN 107365815 A CN107365815 A CN 107365815A CN 201610318784 A CN201610318784 A CN 201610318784A CN 107365815 A CN107365815 A CN 107365815A
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- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
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Abstract
The invention belongs to industrial microbial technology field, and in particular to a kind of new A40926 fermentation feed mediums and feed supplement modulation process.The supplying technicses are a kind of methods that Dalbavancin precursor A40926 is produced by pH feedback supplements, culture starts to add supplemented medium to 40~120h, by adjusting the flow velocity of supplemented medium and NaOH solution, maintenance zymotic fluid remaining sugar concentration is 10~30g/L, pH between 6.0~8.0.This method had both relieved the suppression of high concentration substrate, nutriment is supplemented again so that product can synthesize under Product formation environment preferably, and the yield of purpose product is greatly improved, fermented and cultured 5~7 days, A40926 fermentation titers reach 800~1200mg/L.This technological operation is easy, is easy to amplify, environmental pollution is small, effectively enhances the synthesis of purpose product.
Description
Technical field
The invention belongs to industrial microbial technology field, and in particular to a kind of fermenting and producing A40926 supplemented medium.
Background technology
Dalbavancin is the semi-synthetic glycopeptides that a kind of second generation after vancomycin and teicoplanin has anti-multi-drug resistant bacteria
Class antibiotic, III clinical trial phase is had been enter at present, it is specifically combined with D- alanyls-D-alanine group, so as to
Suppress the synthesis of cell membrane, cause somatic cells because of osmotic pressure effect water swelling until rupture is dead, to gram-positive bacteria
Such as Methicillin resistant Staph. aureus (MRSA), methicillin-sensitivity staphylococcus aureus (MSSA), coagulase-negative staphylococci
(CoNS), streptococcus, penicillin resistant and ceftriaxone streptococcus pneumonia and neisseria gonorrhoeae (Neisseria gonorr
) etc. hoeae it is respectively provided with preferable antibacterial effect.Because Dalbavancin has antibacterial spectrum width, better tolerance, long half time, pair
The advantages that small is acted on, new selection is provided for clinical treatment gram positive bacteria infection.
Dalbavancin synthesis precursor A40926 is the day as caused by Ye Ye villages actinomyces (Nonomuraea sp.) ATCC39727
Right glycopeptide antibiotics, are mainly made up of PA, PB, A, B0 and B1.At present, Dalbavancin precursor A40926 ferments
Technical study and report are seldom.Product is mainly given birth to by the Vicuron Pharmaceuticals drugmakers of Italy by fermenting
Production, its highest fermentation unit reported is 128mg/L.Beltrametti F. et al. (Valine influences production and
complex composition of glycopeptide antibiotic A40926in fermentations of Nonomuraea sp.
ATCC 39727, The Journal of Antibiotics, 2004,57 (1)：33~44) research finds that Valine is A40926
The potential precursor of branch's acyl chain of B0 components, 0.3%L- valines are added in T/2 culture mediums, are obtained in shake flat experiment
Highest 220U/mL total outputs were obtained, but report is only limitted to shaking flask yield.Rational supplemented medium and supplying technicses control
One of key factor of high yield Dalbavancin is obtained, the A of Chinese invention patent application CN 103060405 disclose one kind
A40926 zymotechnique, the technical scheme report the total output that 720mg/L is can reach by flow feeding culture medium.
The content of the invention
In order to improve production antibiotic A40926 fermentation unit, the invention provides a kind of new fermenting and producing A40926's
Supplemented medium.
Fermenting and producing antibiotic A40926 of the present invention supplemented medium, including carbon source, nitrogen source, precursor substance,
Wherein, described carbon source is glucose, and described nitrogen source is corn steep liquor solution, and precursor substance is Valine.
Included in supplemented medium of the present invention：40~90g/L of glucose, corn steep liquor solution 90~180g/L, L- figured silk fabrics ammonia
3~10g/L of acid, and adjust pH to 6.0-8.0.
In supplemented medium of the present invention, glucose content is preferably 50~70g/L, it is still further preferred that 65g/L.
In supplemented medium of the present invention, corn steep liquor solution content is preferably 110~150g/L, it is still further preferred that 120
g/L。
In supplemented medium of the present invention, Valine content is preferably 5~8g/L, it is still further preferred that 6g/L.
In supplemented medium of the present invention, the NaOH solution that the solution used in pH is 0.5~2.0mol/L is adjusted.
In supplemented medium of the present invention, pH to 7.0 is adjusted.
Present invention also offers a kind of fermenting and producing antibiotic A40926 feed supplement modulation process, is specially：Fermented and cultured is extremely
40~120h, continuous stream add supplemented medium to carry out feed supplement, while by adjusting the flow velocity of supplemented medium and NaOH solution,
It is 10~30g/L to make zymotic fluid remaining sugar concentration, and pH is stable between 6.0~8.0, and fermented and cultured puts tank after 5~7 days, detection is
Can.
In feed supplement modulation process of the present invention, the concentration of the NaOH solution is 0.5~2.0mol/L.
In feed supplement modulation process of the present invention, by adjusting supplemented medium flow control zymotic fluid remaining sugar concentration, compared with
Good zymotic fluid remaining sugar concentration is 20~25g/L.
In feed supplement modulation process of the present invention, the pH of fermentation medium is controlled by adjusting NaOH solution flow velocity,
Preferable pH is 6.5~7.5.
Present invention also offers a kind of fermenting and producing A40926 method, specifically comprise the following steps：
A) Shaking culture：The production strain that inclined-plane flat board preserves is inoculated with into shake-flask seed culture medium：Glucose 2%, oat
Powder 2%, tryptone 0.3%, FeSO4·7H2O 0.001%, MnCl2·4H2O 0.001%, ZnSO4·7H2O 0.001%,
PH 7.2,72h, shaking speed 200rpm are cultivated at 25~30 DEG C；
B) seed culture：Shake-flask seed liquid is inoculated in seeding tank, the same shake-flask seed culture medium of seed tank culture base, culture temperature
25~30 DEG C, speed of agitator 180rpm of degree, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.
C) fermented and cultured：After seed culture 72h, seed liquor obtained by step b) is sent out with 8% inoculum concentration culture transferring to fermentation tank
Liquid fermentation and culture is carried out in ferment culture medium, with 25~32 DEG C of cultures, speed of agitator is 120~220rpm, and tank presses 0.05Mpa,
Ventilation ratio 1:1V/V/min；For fermented and cultured to 40~120h, continuous stream adds supplemented medium to carry out feed supplement, while passes through regulation
Supplemented medium and NaOH solution flow velocity, it is 10~30g/L to make zymotic fluid remaining sugar concentration, and pH is stable between 6.0~8.0,
Fermented and cultured puts tank, detection after 5~7 days.
In fermentation method for producing of the present invention, the fermentation medium in above-mentioned steps c) fermented and cultureds is to contain based on one liter
There is the component of following proportioning：Cornstarch 2%~4%, dextrin 1%~2%, glucose 1%~2%, soya-bean oil 0.5%~1% are yellow
Beancake powder 3%~4%, tryptone 1%~1.5%, Valine 0.1%~0.2%, calcium carbonate 0.4%~0.8%, pH 6.0~6.5.
In fermentation method for producing of the present invention, the condition of above-mentioned steps c) fermented and cultureds is preferably：Temperature is 28 DEG C,
Speed of agitator is 180rpm.
In fermentation method for producing of the present invention, described production A40926 strain described in the routine of this area can
Fermenting and producing A40926 strain, preferably Ye Ye villages Bordetella actinomyces (Nonomuraea sp.) ATCC 39727.
In fermentation method for producing of the present invention, the seed liquor of above-mentioned Ye Ye villages actinomyces can by a conventional method will
Obtained from Ye Ye villages actinomyces are cultivated in seed culture medium.Wherein, described seed culture medium can be existing wild
The seed culture medium of village actinomyces, the temperature of seed culture are preferably 28 DEG C.
Feed supplement and fermentation tank culture medium used in the present invention are using conventional real elimination bacterium.
Raw material or reagent used in the present invention is commercially available in addition to special instruction.
It is as follows compared to existing supplemented medium and feed supplement modulation process, beneficial effects of the present invention：
The invention provides a kind of high-efficiency fermenting production antibiotic A40926 supplemented medium and corresponding feed supplement adjusting method
And production method.By the carbon nitrogen source composition proportion and pH fermentation parameters of preferred supplemented medium, that is, pass through pH feedback supplements
The method for producing Dalbavancin precursor A40926, cultivates to 40~120h and starts to add described supplemented medium, meanwhile,
It is 10~30g/L, pH by adjusting supplemented medium and NaOH solution flow acceleration maintenance ferment tank liquid remaining sugar concentration
Between 6.0~8.0, a kind of environment for being more beneficial for Product formation is created, relieves suppression of the high concentration substrate to Product formation
System, so as to which A40926 yield be greatly improved.
A40926 provided by the present invention feed-batch culture based formulas and its feed supplement regulation technique and production method, are greatly improved
A40926 fermentation unit, fermentation total output can reach 800~1200mg/L.Meanwhile the technological operation is simple, it is easy to put
Greatly, environmental pollution is small, has been successfully applied to 5m3In ferment tank incubation, suitable for A40926 scale
Production.
Embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to described embodiment
Among scope.
Embodiment l
The kind Ziye open country village Bordetella actinomyces ATCC 39727 that inclined-plane flat board preserves is inoculated with into shake-flask seed culture medium：Portugal
Grape sugar 2%, oatmeal 2%, tryptone 0.3%, FeSO4·7H2O 0.001%, MnCl2·4H2O 0.001%,
ZnSO4·7H2O 0.001%, pH 7.2,72h, shaking speed 200rpm are cultivated at 28 DEG C.
100mL shake-flask seed liquids are inoculated in into seeding tank, and (30L tanks, liquid amount 60%, culture medium is the same as shake-flask seed culture
Base), 30 DEG C, speed of agitator 180rpm of cultivation temperature, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.Cultivate 72h
Afterwards, with 8% inoculum concentration culture transferring to 50L fermentation tanks, actual liquid amount 30L, cultivated with 28 DEG C, wherein, speed of agitator is
180rpm, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.
Fermentation medium is prepared, cornstarch 4%, dextrin 1.5%, glucose 2%, soya-bean oil 1%, soybean cake powder 4%, egg
The white peptone 1.5% of pancreas, Valine 0.2%, calcium carbonate 0.5%, pH 6.0.
82h is cultivated, remaining sugar concentration in zymotic fluid is detected and is reduced to 15g/L, start stream plus contain glucose 65g/L and pH 7.0
Supplemented medium, by adjusting feed-batch culture base flow rate of acceleration, it is 20~25g/L to maintain zymotic fluid remaining sugar concentration.Fermentation 150
H, by HPLC detect A40926 concentration in zymotic fluid (detection method is recorded in, Microbiol Biotec hnol, 2003,
30：150~156), wherein, A40926 fermentation units are 510mg/L.
Embodiment 2
Other conditions are the same as embodiment 1.
90h is cultivated, the remaining sugar concentration in zymotic fluid is reduced to 10g/L, starts stream plus contains glucose 65g/L and pH 7.0
Supplemented medium, meanwhile, by adjusting the NaOH solution flow velocity of supplemented medium and 1.0mol/L, control zymotic fluid
Remaining sugar concentration is 20~25g/L, and pH is maintained between 6.5~7.0.Fermented 168h, and A40926 in zymotic fluid is detected by HPLC
Concentration, wherein, A40926 fermentation units are 600mg/L.
Embodiment 3
Other conditions are the same as embodiment 1.
80h is cultivated, the remaining sugar concentration in zymotic fluid is reduced to 15g/L, starts stream plus containing glucose 40g/L, corn steep liquor
Solution 180g/L, Valine 10g/L and pH 7.0 supplemented medium, meanwhile, by adjusting supplemented medium and 1.0
Mol/L NaOH solution flow velocity, it is 15~20g/L to control zymotic fluid remaining sugar concentration, and pH is maintained between 6.0~6.5.Hair
Ferment 162h, A40926 concentration in zymotic fluid is detected by HPLC, wherein, A40926 fermentation units are 820mg/L.
Embodiment 4
Other conditions are the same as embodiment 1.
65h is cultivated, the remaining sugar concentration in zymotic fluid is reduced to 25g/L, starts stream plus containing glucose 90g/L, corn steep liquor
Solution 90g/L, Valine 5g/L and pH 7.0 supplemented medium, by adjusting supplemented medium and 1.0mol/L
NaOH solution flow velocity, it is 10~15g/L to control zymotic fluid remaining sugar concentration, and pH is maintained between 7.0~7.5.Ferment 164h,
A40926 concentration in zymotic fluid is detected by HPLC, wherein, A40926 fermentation units are 850mg/L.
Embodiment 5
Other conditions are the same as embodiment 1.
66h is cultivated, the remaining sugar concentration in zymotic fluid is reduced to 25g/L, starts stream plus containing glucose 70g/L, corn steep liquor
Solution 150g/L, Valine 3g/L and pH 7.0 supplemented medium, meanwhile, by adjusting supplemented medium and 1.0mol/L
NaOH solution flow velocity, it is 25~30g/L to control zymotic fluid remaining sugar concentration, and pH is maintained between 7.5~8.0.Fermentation 166
H, A40926 concentration in zymotic fluid is detected by HPLC, wherein, A40926 fermentation units are 880mg/L.
Embodiment 6
Other conditions are the same as embodiment 1.
67h is cultivated, the remaining sugar concentration in zymotic fluid is reduced to 25g/L, starts stream plus containing glucose 50g/L, corn steep liquor
Solution 110g/L, Valine 8g/L and pH 7.0 supplemented medium, meanwhile, by adjusting supplemented medium and 1.0mol/L
NaOH solution flow velocity, it is 25~30g/L to control zymotic fluid remaining sugar concentration, and pH is maintained between 6.5~7.0.Fermentation 168
H, A40926 concentration in zymotic fluid is detected by HPLC, wherein, A40926 fermentation units are 980mg/L.
Embodiment 7
Other conditions are the same as embodiment 1.
Fermentation medium is prepared, cornstarch 3%, dextrin 1%, glucose 1%, soya-bean oil 0.5%, soybean cake powder 3%, egg
The white peptone 1% of pancreas, Valine 0.15%, calcium carbonate 0.5%, pH 6.0.
When fermented and cultured proceeds to 60h, detect remaining sugar concentration in zymotic fluid and be less than 25g/L, start stream plus contain glucose
65g/L, corn steep liquor solution 120g/L, Valine 6g/L and pH 7.0 supplemented medium, meanwhile, pass through to adjust and mend
Expect culture medium and 1.0mol/L NaOH solution flow velocity, it is 25~30g/L to control zymotic fluid remaining sugar concentration, and pH is maintained
Between 7.0~7.5.Ferment 144h, detects A40926 concentration in zymotic fluid by HPLC, A40926 fermentation units are 1058
mg/L。
Embodiment 8
Other conditions are the same as embodiment 1.
Fermentation medium is prepared, cornstarch 2%, dextrin 2%, glucose 1.5%, soya-bean oil 1%, soybean cake powder 4%, egg
The white peptone 1.5% of pancreas, Valine 0.1%, calcium carbonate 0.4%, pH 6.5.
When fermented and cultured proceeds to 60h, detect remaining sugar concentration in zymotic fluid and be less than 20g/L, start stream plus contain glucose
65g/L, corn steep liquor solution 120g/L, Valine 6g/L and pH 7.0 supplemented medium, meanwhile, pass through to adjust and mend
Expect culture medium and 1.0mol/L NaOH solution flow velocity, it is 20~25g/L to control zymotic fluid remaining sugar concentration, and pH is 6.5~7.0
Between.Ferment 142h, detects A40926 concentration in zymotic fluid by HPLC, A40926 fermentation units are 1150mg/L.
Embodiment 9
Other conditions are the same as embodiment 1.
Fermentation medium is prepared, cornstarch 3%, dextrin 1%, glucose 1%, soya-bean oil 0.5%, soybean cake powder 3%, egg
The white peptone 1% of pancreas, Valine 0.15%, calcium carbonate 0.8%, pH 6.0.
When fermented and cultured proceeds to 65h, detect remaining sugar concentration in zymotic fluid and be less than 20g/L, start stream plus contain glucose
65g/L, corn steep liquor solution 120g/L, Valine 6g/L and pH 7.0 supplemented medium, meanwhile, pass through to adjust and mend
Expect culture medium and 1.0mol/L NaOH solution flow velocity, it is 20~25g/L to control zymotic fluid remaining sugar concentration, and pH is 7.0~7.5
Between.Ferment 144h, detects A40926 concentration in zymotic fluid by HPLC, A40926 fermentation units are 1162mg/L.
Embodiment 10
The kind Ziye open country village Bordetella actinomyces ATCC 39727 that inclined-plane flat board preserves is inoculated with into shake-flask seed culture medium：Portugal
Grape sugar 2%, oatmeal 2%, tryptone 0.3%, FeSO4·7H2O 0.001%, MnCl2·4H2O 0.001%,
ZnSO4·7H2O 0.001%, pH 7.2,72h, shaking speed 200rpm are cultivated at 28 DEG C.
200mL shake-flask seed liquids are inoculated in first class seed pot (50L tanks, liquid amount 60%, the same shake-flask seed of culture medium
Culture medium), 30 DEG C, speed of agitator 180rpm of cultivation temperature, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.
After cultivating 72h, with 8% inoculum concentration culture transferring to secondary seed tank (500L tanks, liquid amount 60%, the same shaking flask of culture medium
Seed culture medium), 30 DEG C, speed of agitator 100rpm of cultivation temperature, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.
After secondary seed tank culture 40h, with 8% inoculum concentration culture transferring to 5m3Fermentation tank, actual liquid amount 2.5m3, culture
30 DEG C of temperature, initial speed of agitator 60rpm is until 180rpm, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min.
Fermentation medium configures：Cornstarch 3%, dextrin 1%, glucose 1%, soya-bean oil 0.5%, soybean cake powder 3%, egg
The white peptone 1% of pancreas, Valine 0.15%, calcium carbonate 0.5%, pH 6.5.
When fermented and cultured proceeds to 58h, detection zymotic fluid remaining sugar concentration is less than 20g/L, starts stream plus contains glucose 65
G/L, corn steep liquor solution 120g/L, Valine 6g/L and pH 7.0 supplemented medium, meanwhile, trained by adjusting feed supplement
Base and 1.0mol/L NaOH solution flow acceleration are supported, it is 20~30g/L to maintain zymotic fluid remaining sugar concentration, and pH is 6.5~7.0
Between.Fermented and cultured 144h, A40926 concentration in zymotic fluid is detected by HPLC, A40926 fermentation units are 1180
mg/L。
Embodiment 11
Other conditions are the same as embodiment 10.
When fermented and cultured proceeds to 55h, detection zymotic fluid remaining sugar concentration is less than 20g/L, starts stream plus contains glucose 65
G/L, corn steep liquor solution 120g/L, Valine 6g/L and pH7.0 supplemented medium, meanwhile, trained by adjusting feed supplement
Base and 1.0mol/L NaOH solution flow acceleration are supported, it is 20~25g/L to maintain zymotic fluid remaining sugar concentration, and pH is 7.0~7.5
Between.Fermented and cultured 144h, A40926 concentration in zymotic fluid is detected by HPLC, A40926 fermentation units are 1200
mg/L。
Claims (9)
- A kind of 1. fermenting and producing A40926 supplemented medium, it is characterised in that：Described supplemented medium includes：Grape Sugar 40~90g/L, corn steep liquor 90~180g/L of solution, Valine 3~10g/L, pH are adjusted to 6.0-8.0.
- 2. supplemented medium as claimed in claim 1, it is characterised in that described supplemented medium includes：Glucose 50~70g/L, corn steep liquor 110~150g/L of solution, Valine 5~8g/L, pH are adjusted to 7.0.
- 3. supplemented medium as claimed in claim 1, it is characterised in that described supplemented medium includes：Glucose 65g/L, corn steep liquor solution 120g/L, Valine 6g/L, pH are adjusted to 7.0.
- A kind of 4. fermenting and producing A40926 feed supplement modulation process, it is characterised in that：Fermented and cultured passes through to 40~120h Continuous stream adds supplemented medium to carry out feed supplement, meanwhile, by changing the flow velocity of supplemented medium and NaOH solution, make hair Zymotic fluid remaining sugar concentration is 10~30g/L, and pH is stable between 6.0~8.0.
- 5. feed supplement regulation technique as claimed in claim 4, it is characterised in that the concentration of the NaOH solution is 0.5~2.0 mol/L。
- A kind of 6. fermenting and producing A40926 method, it is characterised in that comprise the following steps：A) Shaking culture：Inclined-plane flat board is preserved into production inoculation and enters shake-flask seed culture medium：Glucose 2%, oatmeal 2%, tryptone 0.3%, FeSO4·7H2O 0.001%, MnCl4H2O 0.001%, ZnSO4·7H2O 0.001%, PH 7.2,72h, shaking speed 200rpm are cultivated at 25~30 DEG C；B) seed culture：Shake-flask seed liquid is inoculated in seeding tank, the same shake-flask seed culture medium of seed tank culture base, culture temperature 25~30 DEG C, speed of agitator 180rpm of degree, tank pressure 0.05Mpa, ventilation ratio 1:1V/V/min；C) fermented and cultured：After seed culture 72h, seed liquor obtained by step b) is sent out with 8% inoculum concentration culture transferring to fermentation tank Liquid fermentation and culture is carried out in ferment culture medium, with 25~32 DEG C of cultures, speed of agitator is 120rpm~220rpm, and tank presses 0.05 Mpa, ventilation ratio 1:1V/V/min；For fermented and cultured to 40~120h, continuous stream adds supplemented medium, meanwhile, pass through regulation Supplemented medium and the flow velocity of NaOH solution make zymotic fluid remaining sugar concentration be 10~30g/L, and pH is stable between 6.0~8.0, Fermented and cultured puts tank, detection after 5~7 days.
- 7. method as claimed in claim 6, it is characterised in that：Fermentation medium in above-mentioned steps c) fermented and cultureds is pressed Percentage by weight meter, includes following components：Cornstarch 2%~4%, dextrin 1%~2%, glucose 1%~2%, soya-bean oil 0.5%~1%, soybean cake powder 3%~4%, tryptone 1%~1.5%, Valine 0.1%~0.2%, calcium carbonate 0.4%~0.8%, and pH 6.0~7.0.
- 8. method as claimed in claim 6, it is characterised in that in step c), the temperature of the fermented and cultured is 28 DEG C.
- 9. method as claimed in claim 6, it is characterised in that in step c), the speed of agitator of the fermented and cultured For 180rpm.
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| CN201610318784.1A CN107365815B (en) | 2016-05-12 | 2016-05-12 | Supplemented medium for fermentation production of A40926 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing A40926 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103060405A (en) * | 2011-10-21 | 2013-04-24 | 上海医药工业研究院 | Fermentation technique of A40926 |
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- 2016-05-12 CN CN201610318784.1A patent/CN107365815B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103060405A (en) * | 2011-10-21 | 2013-04-24 | 上海医药工业研究院 | Fermentation technique of A40926 |
Non-Patent Citations (3)
| Title |
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| NINA GUNNARSSON等: "Production of the glycopeptide antibiotic A40926 by Nonomuraea sp. ATCC 39727: influence of medium composition in batch fermentation", 《J IND MICROBIOL BIOTECHNOL.》 * |
| 白坤: "《玉米淀粉工程技术》", 31 January 2012, 北京：中国轻工业出版社 * |
| 陈昌发 等: "A40926高产菌株的选育及发酵工艺优化", 《中国抗生素杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing 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 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| 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 |
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| CN107365815B (en) | 2021-10-29 |
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