CN106591400A - Material supplementing method for reducing viscosity of gentamicin C1a fermentation liquid - Google Patents
Material supplementing method for reducing viscosity of gentamicin C1a fermentation liquid Download PDFInfo
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- CN106591400A CN106591400A CN201710133495.9A CN201710133495A CN106591400A CN 106591400 A CN106591400 A CN 106591400A CN 201710133495 A CN201710133495 A CN 201710133495A CN 106591400 A CN106591400 A CN 106591400A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/44—Preparation of O-glycosides, e.g. glucosides
- C12P19/46—Preparation of O-glycosides, e.g. glucosides having an oxygen atom of the saccharide radical bound to a cyclohexyl radical, e.g. kasugamycin
- C12P19/48—Preparation of O-glycosides, e.g. glucosides having an oxygen atom of the saccharide radical bound to a cyclohexyl radical, e.g. kasugamycin the cyclohexyl radical being substituted by two or more nitrogen atoms, e.g. destomycin, neamin
- C12P19/485—Having two saccharide radicals bound through only oxygen to non-adjacent ring carbons of the cyclohexyl radical, e.g. gentamycin, kanamycin, sisomycin, verdamycin, mutamycin, tobramycin, nebramycin, antibiotics 66-40B, 66-40D, XK-62-2, 66-40, G-418, G-52
Abstract
The invention relates to a material supplementing method for reducing viscosity of a gentamicin C1a fermentation liquid, and belongs to the field of fermentation engineering, in the whole fermentation process only control of supplementing of two materials of carbon and nitrogen is performed in the method, reducing sugar concentration in a fermentation pot is controlled in 1-20g / L, when the reducing sugar concentration is lower than 5g / L, a continuous flow adding method is used for supplementing the carbon, when the reducing sugar concentration is higher than 20g / L, the supplementing of the carbon is stopped, the rate for the supplementing of the carbon is adjusted according to real-time off-line determined reducing sugar concentration and fermentation liquid viscosity; amino nitrogen in the fermentation pot is controlled in 20-60mg / mL, when the amino nitrogen concentration is lower than 30mg / mL, the continuous flow adding method is used for supplementing the nitrogen, when the amino nitrogen concentration is higher than 60mg / mL, the supplementing of the nitrogen is stopped, and the rate for the supplementing of the nitrogen is adjusted according to real-time off-line determined amino nitrogen concentration and fermentation liquid viscosity. The method is simple in process, can obviously reduce the viscosity of the fermentation liquid and improve the oxygen transfer, and has an important effect on increasing of the yield of gentamicin.
Description
Technical field
It is the invention belongs to fermentation engineering field, and in particular to the fermenting and producing of gentamycin, more particularly to a kind of
Reduce the feed process of Gentamicin C1a fermentation liquid viscosity.
Background technology
Gentamicin C1a is domestic initiation, possesses independent intellectual property rights as a kind of important aminoglycoside antibioticss
The semi-synthetic new drug clothing of a class for meter Xing parent nucleus.Tradition prepares the method for C1a is celebrated from many components using resin isolation technics
C1a one-components are extracted in big mycin, as structure is similar between each component, physicochemical properties are close, result in extraction cost
High, on market, high-purity C 1a prices remain high.
As many component gentamycin fermentation technologys are more, current one-component Gentamicin C1a fermentation technology is mainly used for reference
Many component gentamycin fermentation technologys, on the premise of big technique is constant, adjust little technological parameter, to improve gentamycin
The yield of C1a.But in actual process control process due to used in a large number the stickiness such as organic nitrogen source and starch, Semen Maydis powder compared with
Big raw material, result in that fermentation later stage viscosity is excessive, and viscosity is one of important indicator of culture medium physical property, and it directly affects oxygen
The diffusion of transmission, nutritional labeling, inorganic salt, somatomedin etc., so as to affect the absorption of the breathing of cell, nutritional labeling, finally
Cause to affect the formation of target product.Therefore need to take measures in gentamycin sweat to reduce fermentation liquid viscosity, carry
High efficiency.Mend the passive measure such as carbon to improve the increase of middle and late stage viscosity frequently with moisturizing in gentamycin real attenuation technique
Caused oxygen is limited, but the problems such as suppression Product formation can be produced.For example, the conventional glucose for mending carbon using one-component,
In gentamycin carbon metablism Research Literature report, the glucose of high concentration has strong inhibitory action to gentamycin synthesis,
But although glucose has inhibitory action to antibiotic synthesis, while and cell growth required carbon source, researcher attempts
By adding the precursor of gentamycin shunt metabolism come derepression, after having attempted, have found that while that these materials can be thin
Born of the same parents effectively absorb, but still can not release the resistance inhibitor action of glucose.Similar variety of problems, in fermenting and producing Gentamicin C1a
During, because how the excessive yield that drastically influence Gentamicin C1a of fermentation liquid viscosity, improve fermentation technology, be allowed to
On the premise of fermentation level is not affected, later stage viscosity is reduced, improve yield, be problem demanding prompt solution.
The content of the invention
For the problem and shortage in above-mentioned gentamycin fermenting and producing, the present invention provides a kind of reduction Gentamicin C1a
The feed process of fermentation liquid viscosity, the method improve fermentation liquid viscosity, Jin Ergai by feed change and control process
The transmission of kind middle and late stage oxygen improves fermentation titer.
A kind of feed process for reducing Gentamicin C1a fermentation liquid viscosity, it is characterised in that：Whole sweat only enters
Row is mended carbon and mends two kinds of control of additive raw material of nitrogen：
Mend carbon control：In fermentation tank, in 1-20g/L, in fermentation tank is determined, concentration of reduced sugar is less than 5g/L for concentration of reduced sugar control
Shi Caiyong continuous streams add feed profile to start supplementary carbon source, stop supplementary carbon source when concentration of reduced sugar is higher than 20g/L；Wherein,
Mend carbon speed to be adjusted according to the concentration of reduced sugar value and fermentation liquid k value of real-time determined off-line：
When concentration of reduced sugar value is higher than 5g/L,,
Rate unit is in terms of kg/h；
When concentration of reduced sugar value is less than 5g/L,, rate unit is in terms of kg/h；
Mend nitrogen control：In fermentation tank, in 20-60mg/mL, in fermentation tank is determined, amino nitrogen is less than 30mg/ for amino nitrogen control
Add feed profile to start to supplement nitrogen source using continuous stream during mL, stop supplementing nitrogen source when amino nitrogen is higher than 60mg/mL；Its
In, mend nitrogen speed and be adjusted according to the amino nitrogen value and fermentation liquid k value of real-time determined off-line：
When amino nitrogen value is higher than 30mg/mL,,
Rate unit is in terms of kg/h；
When amino nitrogen value is less than 30 mg/mL,, rate unit is in terms of kg/h.
Further, the composition and its mass percent of the carbon source is respectively：Glucose 30-40%, maltose 5-10%
With D- xylose 0.5-2.0%, remaining is water.
Further, the composition and its mass percent of the nitrogen source is respectively：Carbamide 10-15%, ammonium sulfate 15-20%,
Semen Maydis pulp 0.5-1.5% and yeast extract powder 1-3%, remaining is water.
Further, the nitrogen source is that carbamide, ammonium sulfate, Semen Maydis pulp and yeast extract powder are dissolved in sterilized water, is prepared
Into solution, then pH value of solution is adjusted to 8.0-9.0 with sodium hydroxide, be obtained after filtration sterilization.
Beneficial effects of the present invention：
1st, the present invention only with benefit carbon and mends two kinds of control of additive raw material of nitrogen in whole sweat, relatively conventional feed profile, this
Invented technology is simply effective, by adjusting the parameters such as component ratio, feed supplement time and the feed rate of carbon source and nitrogen source, on the one hand
Alleviate because of the not enough phenomenon being suppressed with the caused thalli growth metabolism such as intermediate accumulation of nutrition supply, be thalline life
It is long to provide energy, maintain microbial activity；On the other hand, feed process of the present invention, reduces fermentation liquid viscosity, fermentation
In liquid, fermentation liquid viscosity reduces 1 times, and potency averagely increases 260u/mL, improves the mixing transmission effect of oxygen, control and guiding
The incubation of producing strains, makes the biochemical metabolism activity of middle and late stage develop towards the direction for being conducive to product accumulation, yield highest
63% is improve, biological value highest improves 40%, be a kind of effective feed process.
2nd, during carbon is mended, carbon source selects glucose, maltose and D- xyloses to the present invention, and wherein glucose is in growth generation
Thank and play an important role with energy provider's mask, but its synthesis to gentamycin exists and suppresses, the appropriate maltose of addition with
D- xyloses alleviate this suppression to a certain extent.During the fermentation, in the case of glucose content abundance relatively, Fructus Hordei Germinatus
The metabolism of sugar is more slow, by inducing, glucose repression and glucose inactivate three kinds of regulatory mechanisms and controlled, in fermentation liquid,
The presence induction maltase of maltose and the synthesis of maltose permease, in the presence of relevant enzyme, maltose and D- xyloses are sent out
Solution estranged or change of configuration, and then during may participate in carbohydrate metabolism, change microbial environment, reduce fermentation viscosity, promote
Cell is bred.
3rd, the present invention contains organic nitrogen source and inorganic nitrogen-sourced in mending the nitrogen source composition of nitrogen during nitrogen is mended simultaneously,
In suitable control fermentation intermediary and later stages fermentation liquid while organic nitrogen source, the inorganic nitrogen-sourced synthesis to Gentamicin C1a is added in right amount
It is favourable, this is because inorganic nitrogen-sourced be difficult to be converted into tropina for thalline, it both ensure that relatively lean in organic nitrogen source
Amidized needs in the case of weary, while and will not stimulate the growth of mycelia, therefore Inorganic Ammonium and the mutually auxiliary phase of control organic nitrogen source
Into the improvement to component in gentamycin fermentation is very strong.Mended by the way of continuous stream adds on this basis
Material, it is to avoid after in causing environmental catastrophe to change the impact brought to bacterial metabolism, effectively can slow down in addition because of once a large amount of additions
Phase, because of the decline of the caused fermentable sugars concentration of the not enough institute of relevant enzyme apparent activity, greatly improves fermentation level.Feed supplement, feed supplement speed
Rate is complemented each other with feed profile, is played a role jointly during the fermentation, reduces the viscosity of fermentation liquid, improves gentamycin
Yield.
Description of the drawings
Fig. 1 is fermentation liquid viscosity change comparison diagram in fermentation period in embodiment 1 and reference examples 1；
Fig. 2 is fermentation liquid potency change comparison diagram in fermentation period in embodiment 1 and reference examples 1.
Specific embodiment
A kind of feed process for reducing Gentamicin C1a fermentation liquid viscosity, whole sweat are only carried out mending carbon and mend nitrogen
Two kinds of control of additive raw material, i.e., start timing from fermentation, reducing sugar, amino nitrogen and viscosity in determining fermentation liquid every 4 hours, Ran Hougen
Result adjusts feed supplement and feed rate according to surveying and determination.Whole sweat only includes benefit carbon and mends two kinds of control of additive raw material of nitrogen：
Mend carbon control：In fermentation tank, concentration of reduced sugar is controlled in 1-20g/L, when in fermentation tank is determined, concentration of reduced sugar is less than 5g/L
Supplementary carbon source is started using continuous stream plus feed profile, the composition and its mass percent of the carbon source are respectively：Glucose 30-40%,
Maltose 5-10% and D- xylose 0.5-2.0%, remaining is water.Stop mending carbon when concentration of reduced sugar is higher than 20g/L.Set up and mend carbon speed
Model, i.e., when concentration of reduced sugar value is higher than 5g/L,；
When concentration of reduced sugar value is less than 5g/L,, rate unit is in terms of kg/h；
Mend nitrogen control：In fermentation tank, in 20-60mg/mL, in fermentation tank is determined, amino nitrogen is less than 30mg/ for amino nitrogen control
Feed profile is added to start to supplement nitrogen source using continuous stream during ml, the composition and its mass percent of the nitrogen source are respectively：Carbamide
10-15%, ammonium sulfate 15-20%, Semen Maydis pulp 0.5-1.5% and yeast extract powder 1-3%, remaining is water.When amino nitrogen is higher than
Stop mending nitrogen during 60mg/mL.Set up feed rate model, i.e., when amino nitrogen value is higher than 30 mg/mL,；When amino nitrogen value is less than 30 mg/mL
When,, rate unit is in terms of kg/h.
Below by specific embodiment, the present invention will be further explained.
Embodiment 1
First order seed culture：In 2m3Fed intake according to composition proportion in table 1 in seed tank.First primary-seed medium is gone out
Bacterium, cooling, using filtrated air pressurize, are then inoculated with differential manometer and for 1L cultured shaking flask kind liquid to access first class seed pot training
Support, during 0.04 ~ 0.08Mpa of tank pressure；33 ~ 38 DEG C of tank temperature；Air mass flow 0.7：1 ；Rotating speed is 150rpm；PH value 6.0-
8.0；Incubation time 45h.21%, pH value is 7.0 to cultured primary seed solution cell concentration, without living contaminantses.
Secondary seed culture：In 15m3Fed intake according to composition proportion in table 1 in culture medium.First by secondary seed culture
Base sterilizes, cooling, using filtrated air pressurize, then cultured primary seed solution is all moved into secondary seed pipe and is trained
Support.During 0.04 ~ 0.08Mpa of tank pressure；33 ~ 38 DEG C of tank temperature；Air mass flow 0.5：1~ 1：1；Rotating speed is 100rpm；PH value
6.0-8.0；Incubation time 43h.30%, pH value is 7.0 to cultured primary seed solution cell concentration, without living contaminantses.
Fermentation culture：In 60m3Feed intake according to proportioning in table 1 in culture medium.First by medium sterilization, cooling, using aseptic
Then cultured secondary seed solution is all moved into and is cultivated in fermentation tank by air pressurize.During tank pressure 0.04 ~
0.08Mpa；33 ~ 38 DEG C of tank temperature；Air mass flow 0.5：1~ 1：1；Rotating speed is 100-150rpm；PH value 6.0-8.0.During also
Raw sugar concentration maintains 1-10g/L；Fermentation period is 110h, and it is 35% to put tank bacterium dense, and fermentation titer is 783u/ml, pH value 7.5.
Table 1：Test recipe and proportioning
Note：In table, % is mass percent.
Reducing sugar, amino nitrogen, viscosity and product potency are determined in sweat, is detected once every 4h, then according to inspection
Survey result adjustment feed rate.Whole sweat is only by mending carbon and mending two kinds of control of additive raw material of nitrogen：
Mend carbon control：In fermentation tank, in 1-20g/L, in fermentation tank is determined, concentration of reduced sugar is less than 5g/L for concentration of reduced sugar control
Shi Caiyong continuous streams add feed profile to start supplementary carbon source, stop supplementary carbon source when concentration of reduced sugar is higher than 20g/L；Wherein,
Mend carbon speed to be adjusted according to the fermentation liquid k value of determined off-line：When concentration of reduced sugar value is higher than 5g/L, feed rate
（kg/h）=（Actual measurement concentration of reduced sugar value-k value/1000-5）* fermentating liquid volume (m3)*10kg/h；When concentration of reduced sugar value
During less than 5g/L, feed rate（kg/h）=fermentating liquid volume (m3)*10kg/h；Wherein, mend carbon speed=current fermentation volume *
10kg/h；
The composition and its mass percent of above-mentioned supplementary carbon source is respectively：Glucose 30%, maltose 10% and D- xyloses 2.0%, its
Yu Weishui.
Mend nitrogen control：In fermentation tank, in 20-60mg/mL, in fermentation tank is determined, amino nitrogen is less than for amino nitrogen control
Add feed profile to start to supplement nitrogen source using continuous stream during 30mg/ml, stop supplementing nitrogen when amino nitrogen is higher than 60mg/mL
Source；Wherein, mend nitrogen speed to be adjusted according to the amino nitrogen and k value of determined off-line：When amino nitrogen value is higher than 30
During mg/ml, nitrogen speed is mended（kg/h）=（Actual measurement amino nitrogen value+k value/1000-30）* fermentating liquid volume * 2；Work as amino
When nitrogen concentration value is less than 30 mg/ml, nitrogen speed is mended（kg/h）=fermentating liquid volume * 20.
The nitrogen source is by the carbamide, ammonium sulfate, Semen Maydis pulp and yeast extract powder being dissolved in sterilized water, being configured to
Solution, then pH value of solution is adjusted to 8.0-9.0 with sodium hydroxide, it is obtained after filtration sterilization.Wherein, the mass percent of carbamide is
10%, the mass percent of ammonium sulfate is 15%, and the mass percent of Semen Maydis pulp is 0.5% and the mass percent of yeast extract powder
For 3%.
Embodiment 2
First order seed culture, secondary seed culture and fermentation culture process are same as Example 1, in the control of additive raw material stage, used
Mend carbon carbon source be：Glucose 40%, maltose 5% and D- xyloses 2.0%.
It is used mend nitrogen nitrogen source be：Carbamide 15%, ammonium sulfate 20%, Semen Maydis pulp 1.5% and yeast extract powder 1%.
Reference examples
First order seed culture, secondary seed culture and fermentation culture process are same as Example 1, but in the control of additive raw material stage, point
Batch fed-batch, feed supplement time are as follows with feed supplement amount：
Fermentation starts first time feed supplement during 24h：Fill into 5-10% complete feeds；
Fermentation starts second feed supplement during 36h：Fill into 5-10% complete feeds；
Fermentation starts third time feed supplement during 44h：Fill into 3-5% complete feeds；
Fermentation starts the 4th feed supplement during 64h：Fill into 5-10% complete feeds；
Afterwards every 10h moisturizings 10% to fermentation ends.
Wherein, the % refers to the percent by volume of benefit amount and fermentation liquid；Complete feed formula is as shown in table 2 below.
Table 2：Complete feed formula in reference examples
To above-described embodiment 1, embodiment 2 and obtained by reference examples, fermentation liquid carries out quality evaluation, from potency, cell concentration, fermentation
The index such as process viscosity and fermentation index is analyzed, wherein, potency refers to concentration of the antibiotic in fermentation liquid, anti-for weighing
The effective ingredient and performance of raw element.As a result it is as shown in table 3 below.
Table 3：The quality evaluation of fermentation liquid
Note：In table, % is mass percent.
As can be seen from Table 3, in the case where fermentation period and cell concentration are more or less the same, 2 institute of embodiment 1 and embodiment
The viscosity maximum for obtaining fermentation liquid drops to 2000cp by conventional 4000cp, and speed and the efficiency of oxygen transmission strengthen so that bacterium
Bulk-growth faster metabolism, causes its potency, fermentation total output and fermentation index to increased, and relative to reference examples, potency is put down
Increase 260u or so per mL, fermentation total output highest increases by 7,500,000,000 units, and fermentation index averagely improves 0.04 hundred million/m3/h, celebrates
Big mycin yield averagely improves 60%.Totally apparently, under identical fermentation period, the fermentation liquid of relative comparison example, embodiment 1
Less with the fixed cost that embodiment 2 is put on specific yield, economic benefit is higher.
The present invention further carries out real-time monitoring to the viscosity and potency of fermentation liquid in embodiment 1 and reference examples, observes
Viscosity and potency change in whole fermentation period, viscosity result of variations is as shown in figure 1, using feed process of the present invention
Before fermentation, in 24h, viscosity change is more or less the same the reference examples 1 of embodiment 1 and conventional method, fermentation liquid in reference examples 1 after 24h
Viscosity starts quick increase, and in fermentation period is afterwards consistently greater than embodiment 1, last viscosity up to 4000cp, wherein,
Relatively reduce in ferment middle viscosity rate of change, this is to alleviate sticking in fermentation liquid to a certain extent due to the feed supplement for adding
Degree change.And in embodiment, fermentation liquid viscosity slowly increases after 24h, tend towards stability in fermentation middle and late stage afterwards, final viscosity
Up to 2000cp.By contrast, using the reference examples of conventional feed process, its viscosity fluctuations is larger, is entirely fermenting
In journey, viscosity is above embodiment, and peak value is up to 4000cp, higher than embodiment viscosity about 1 times, and maintains viscosity persistently to increase
The time of gesture is longer, until fermentation period terminates, viscosity is just presented stable tendency.Potency changes as shown in Fig. 2 in earlier fermentation
Fermentation liquid potency change in reference examples 1 and embodiment 1 is more or less the same, and after 24h, in embodiment 1, fermentation liquid potency is high all the time
In reference examples 1, two kinds of fermentation liquids present of short duration stable tendency in ferment middle, and embodiment 1 is increased with higher afterwards
Speed sustainable growth, and this growth trend continues up to fermentation ends, this is, due to control of additive raw material, to make viscosity in fermentation liquid
Improved etc. physical characteristics, promoted the growth metabolism of Gentamicin C1a producing strains.As can be seen here, feed supplement of the present invention
Method is highly effective to reducing fermentation liquid viscosity, increased fermentation titer, improves the yield of Gentamicin C1a.
Embodiment of the present invention is illustrative, does not limit protection scope of the present invention, the protection of the present invention with this
Scope is defined by claims, on the premise of without departing from essence of the invention and spirit, the equal replacement done by the present invention
Or modification, belong to protection scope of the present invention.
Claims (4)
1. it is a kind of reduce Gentamicin C1a fermentation liquid viscosity feed process, it is characterised in that：Whole sweat is only mended
Carbon and benefit two kinds of control of additive raw material of nitrogen：
Mend carbon control：In fermentation tank, in 1-20g/L, in fermentation tank is determined, concentration of reduced sugar is less than 5g/L for concentration of reduced sugar control
Shi Caiyong continuous streams add feed profile to start supplementary carbon source, stop supplementary carbon source when concentration of reduced sugar is higher than 20g/L；Wherein,
Mend carbon speed to be adjusted according to the concentration of reduced sugar value and fermentation liquid k value of real-time determined off-line：
When concentration of reduced sugar value is higher than 5g/L,,
Rate unit is in terms of kg/h；
When concentration of reduced sugar value is less than 5g/L,, rate unit is in terms of kg/h；
Mend nitrogen control：In fermentation tank, in 20-60mg/mL, in fermentation tank is determined, amino nitrogen is less than 30mg/ for amino nitrogen control
Add feed profile to start to supplement nitrogen source using continuous stream during mL, stop supplementing nitrogen source when amino nitrogen is higher than 60mg/mL；Its
In, mend nitrogen speed and be adjusted according to the amino nitrogen value and fermentation liquid k value of real-time determined off-line：
When amino nitrogen value is higher than 30mg/mL,,
Rate unit is in terms of kg/h；
When amino nitrogen value is less than 30 mg/mL,, rate unit is with kg/h
Meter.
2. the feed process of Gentamicin C1a fermentation liquid viscosity is reduced as claimed in claim 1, it is characterised in that：The carbon
The composition and its mass percent in source is respectively：Glucose 30-40%, maltose 5-10% and D- xylose 0.5-2.0%, remaining is
Water.
3. the feed process of Gentamicin C1a fermentation liquid viscosity is reduced as claimed in claim 1, it is characterised in that：The nitrogen
The composition and its mass percent in source is respectively：Carbamide 10-15%, ammonium sulfate 15-20%, Semen Maydis pulp 0.5-1.5% and yeast are leached
Powder 1-3%, remaining is water.
4. the feed process of Gentamicin C1a fermentation liquid viscosity is reduced as claimed in claim 3, it is characterised in that：The nitrogen
Source is by carbamide, ammonium sulfate, Semen Maydis pulp and yeast extract powder being dissolved in sterilized water, solution being configured to, then is used sodium hydroxide
Adjustment pH value of solution is obtained after filtration sterilization to 8.0-9.0.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107523597A (en) * | 2017-09-05 | 2017-12-29 | 河南仁华生物科技有限公司 | A kind of feed process for improving gentamicin fermentation unit and changing its component composition |
| CN110551660A (en) * | 2019-09-17 | 2019-12-10 | 华东理工大学 | synthetic culture medium and preparation method and application thereof |
| CN110628850A (en) * | 2019-09-23 | 2019-12-31 | 华东理工大学青岛创新研究院 | Method for semi-continuously producing gentamicin C1a based on control of specific growth rate |
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| CN1103430A (en) * | 1994-05-16 | 1995-06-07 | 杨都 | Process for producing raw material drug of gentamicin |
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| CN1103430A (en) * | 1994-05-16 | 1995-06-07 | 杨都 | Process for producing raw material drug of gentamicin |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107523597A (en) * | 2017-09-05 | 2017-12-29 | 河南仁华生物科技有限公司 | A kind of feed process for improving gentamicin fermentation unit and changing its component composition |
| CN107523597B (en) * | 2017-09-05 | 2021-06-29 | 河南仁华生物科技有限公司 | Material supplementing method for improving gentamicin fermentation unit and changing component composition of gentamicin fermentation unit |
| CN110551660A (en) * | 2019-09-17 | 2019-12-10 | 华东理工大学 | synthetic culture medium and preparation method and application thereof |
| CN110628850A (en) * | 2019-09-23 | 2019-12-31 | 华东理工大学青岛创新研究院 | Method for semi-continuously producing gentamicin C1a based on control of specific growth rate |
| CN110628850B (en) * | 2019-09-23 | 2021-12-07 | 华东理工大学青岛创新研究院 | Method for semi-continuously producing gentamicin C1a based on control of specific growth rate |
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