CN101560535B - Process for producing abamectin by feeding glucose fermentation based on metabolizing parameters OUR - Google Patents
Process for producing abamectin by feeding glucose fermentation based on metabolizing parameters OUR Download PDFInfo
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Abstract
The invention relates to a process for producing abamectin by feeding glucose fermentation based on metabolizing parameters OUR, belonging to the technical field of bio-fermentation. The method is characterized by comprising the following processing steps of: (1) sub-culturing streptomyces avermitilis into a 250ml shake flask for primary seed cultivation; (2) sub-culturing seeds obtained from step(1) into a 15L seed tank for secondary seed cultivation; and (3) sub-culturing the seeds obtained from step (2) into a 50L fermentation tank for fermentation cultivation, measuring OUR value of exhau st gas in the fermentation process in real time and conducting glucose feeding according to the OUR value. As the process is reasonably designed, the cost is reduced, the thalli senescence in the fermentation process is effectively delayed, and the titer of abamectin is improved by about 20 percent, thereby obtaining high yield by effectively utilizing raw materials.
Description
Technical field
The invention belongs to technical field of biological fermentation, be specifically related to a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology.
Background technology
Avrmectin is a kind of nerve poison; Its mechanism is the GABA acceptor that acts on insect synapse or neuromuscular synapse, and the information transmission of nerve ending promptly excites nerve ending to emit neurotransmission suppressor factor γ-An Jidingsuan (GABA) in the interference insect body; Impel the chloride channel of GABA gate to prolong open; Chloride channel is had activation, and a large amount of cl ionss pour in and cause the hyperpolarization of neu current potential, cause neu to be in holddown; Thereby getting in touch of block nerves tip and muscle makes insect paralysis, food refusal, death.Because of its mechanism of action uniqueness, so do not have cross resistance with medicament commonly used.Except that the chloride channel of GABA acceptor control, Avrmectin can also influence the chloride channel of other ligand controls, can induce the irreversible increase of the myofibrillar film conduction of the innerv locust of no GABA like Ivermectin HCL (avermectin derivatives).
Avid kyowamycin carries out along with metabolic during the fermentation, and nutritive substance constantly consumes, and various by products accumulate gradually.In the fermentation middle and later periods, constantly reduce owing to supply with the nutritive substance of thalline, final performance is tired and is increasesd slowly, and bacterial metabolism is poor, and OUR (oxygen uptake rate) and CER (CO2 thinning ratio) have downtrending in various degree.See the loose aging and phenomenons such as formation of vacuoles and self-dissolving of main performance cenobium from bacterium shape.On biochemical indicator, mainly show available reducing sugar low (less than 1%), amino nitrogen content raises, characteristics such as pH rise.Producing the of paramount importance reason of these phenomenons is exactly because the energy deficiency of supply bacterial metabolism causes.Therefore, improve the fermentation level of Avrmectin, prior art is mainly through mending sugar.Mending sugared purpose mainly is:
(1) mending sugar can increase bacterial metabolism vigor (OUR, CER performance obviously increase), and the delay thalline is old and feeble, prolongs fermentation period, has improved the utilization ratio of production phase, and promptly effectively increase production phase.
(2) thus mend sugar and can suitably keep or increase fermentation volume and increase fermentation total hundred million.
(3) mend to improve behind the sugared process optimization and tire the same period, more can directly improve production level.
(4) but mend sugar optimization production technology to reduce total hundred million costs of unit.
The at present abamectin fermented process method of taking to mend sugar is reported also seldom, though these methods are to a certain extent to promoting the active influence of having tired of Avrmectin.Yet, at present because of the rise of raw materials for production price, make that the cost of producing Avrmectin is high, certainly will influence the enthusiasm of producing Avrmectin once more.In the feed supplement experimentation, need confirm the speed and the consumption of feed supplement,, will bring serious negative consequence to the result of fermenting if the feedback index is not obvious or clash based on feed supplement time and speed and thalline based on the sweat index.
Summary of the invention
To the problem that exists in the prior art, the present invention is through mending sugar operation based on the value of metabolizing parameters OUR in the Avid kyowamycin fermenting process, and design provides a kind of technical scheme that improves the fermentation that Avrmectin tires.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology, it is characterized in that comprising following process step:
(1) the deinsectization streptomycete culture transferring is shaken to 250ml carries out first order seed in the bottle and cultivate;
(2) carrying out secondary seed in seed liquor culture transferring to the 15L seeding tank that step (1) is obtained cultivates;
(3) seed liquor culture transferring to the 50L fermentor tank that step (2) is obtained carries out fermentation culture, The real time measure fermentation tail gas OUR value in the fermenting process, and the sugar operation is mended in variation according to the OUR value.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that the first order seed culture condition is in the step (1): 28 ℃ of temperature; Under 250 rev/mins of the shaking speed; Cultivated 30-40 hour, the first order seed substratum that shakes in the bottle contains: W-Gum 28-32g/L, steeping water 3-7g/L, yeast extract paste 13-17g/L, KH
2PO
42-6g/L and zero(ppm) water, and to transfer PH be 7.0-7.2, is preferably: W-Gum 29-31g/L, steeping water 4-6g/L, yeast extract paste 14-16g/L, KH
2PO
43-5g/L and zero(ppm) water.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that the secondary seed culture condition is in the step (2): 28 ℃ of temperature; 200 rev/mins of rotating speeds, pressure 0.05MPa, ventilating ratio are under the 0.5vvm; Cultivated 36-48 hour, secondary seed medium contains in the seeding tank: W-Gum 28-32g/L, steeping water 3-7g/L, yeast extract paste 13-17g/L, KH
2PO
42-6g/L and zero(ppm) water, and to transfer PH be 7.0-7.2, is preferably: W-Gum 29-31g/L, steeping water 4-6g/L, yeast extract paste 14-16g/L, KH
2PO
43-5g/L and zero(ppm) water.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that fermentation culture conditions is in the step (3): under 28 ℃ of temperature; Cultivated 13 days, the fermentation cylinder for fermentation substratum contains: W-Gum 110-130g/L, yeast powder 13-17g/L, bean cake powder 3-7g/L, groundnut meal 3-7g/L, KH
2PO
43-7g/L and zero(ppm) water, and to transfer pH be 7.0-7.2, is preferably: W-Gum 115-125g/L, yeast powder 14-16g/L, bean cake powder 4-6g/L, groundnut meal 4-6g/L, KH
2PO
44-6g/L and zero(ppm) water.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology, it is characterized in that adopting in the step (3) stream to add the sugared mode of benefit and mend sugared operation.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that fermentation is after 130-150 hour in the step (3); Be OUR value when beginning occur to descend, begin to mend the sugar operation, mending the sugar operation, to adopt weight concentration be the glucose solution of 15-45%; Mending sugared speed is 7-27ml/h, makes the OUR value be controlled at 9-14mmol/Lh.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology, mend the sugar operation after it is characterized in that fermenting 144 hours in the step (3), benefit sugar employing concentration is the glucose solution of 20-40%; Fermentation 144-168 hour, mending sugared speed was 7-13ml/h, 169-193 hour; Mending sugared speed is 10-17ml/h, and 194-218 hour, mending sugared speed was 10-30ml/h; 219-243 hour, mending sugared speed was 7-27ml/h, made the OUR value be controlled at 10-13mmol/Lh.
Described a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology, it is characterized in that mending sugared speed was 8-12ml/h fermentation 144-168 hour; 169-193 hour; Mending sugared speed is 10-16ml/h, and 194-218 hour, mending sugared speed was 12-30ml/h; 219-243 hour, mending sugared speed was 8-24ml/h.
Of the present invention a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; Reasonable in design, reduced production cost, effectively delayed the aging of thalline during the fermentation; That improves Avrmectin tires about 20%, thereby effectively utilizes raw material to obtain high yield.
Description of drawings
The Changing Pattern of Fermentation Process of Parameter such as Figure 150 L fermenting process total reducing sugar, reducing sugar;
Fig. 2 mends sugared speed and thalline aging degree and the Avrmectin graph of a relation between tiring;
Fig. 3 mends sugared mode for three kinds and mends the sugar operation relatively;
OUR parameter Changing Pattern in the conventional fermenting process of Fig. 4;
Fig. 5 mends in the sugared process and the comparison diagram that batch carried out of not mending sugar according to fermentation;
Fig. 6 mends the sugar strategy fermentation on 2 tons of pilot scale jars amplification checking result.
Embodiment
Below further specify the present invention through embodiment and experimental example; Seeding tank and fermentor tank are produced by Guoqiang Biochemical Engineering Equipment Co., Ltd., Shanghai in the invention; Exhaust analyzer is the biological exhaust gas analysis system analysis (Chongqing Hartmann measuring instrument device ltd) of PS6000 type, and OUR is the thalline oxygen uptake rate in the invention, and CER is carbonic acid gas (CO2) release rate; RQ is a respiratory quotient, RQ=CER/OUR.
The preparation slant medium: yeast extract paste 0.1%, SANMALT-S 0.1%, Tryptones 0.2%, agar powder 2%, glucose 2%, surplus are zero(ppm) water, and transfer pH to 7.2, and sterilize.
Preparation seed culture medium (comprising the firsts and seconds seed culture medium): W-Gum 28g/L, steeping water 3g/L, yeast extract paste 13g/L, KH
2PO
42g/L, with zero(ppm) water configuration, and to transfer PH be 7.0, and sterilize, and is preferably: W-Gum 29g/L, steeping water 5g/L, yeast extract paste 15g/L, KH
2PO
44g/L, with zero(ppm) water configuration, and to transfer PH be 7.1, and sterilize.
Preparation fermention medium: W-Gum 110g/L, yeast powder 13g/L, bean cake powder 3g/L, groundnut meal 3g/L, KH
2PO
43g/L, with zero(ppm) water configuration, and to transfer PH be 7.0, and sterilize, and is preferably: W-Gum 120g/L, yeast powder 15g/L, bean cake powder 5g/L, groundnut meal 5g/L, KH
2PO
45g/L, with the zero(ppm) water configuration, and accent PH is 7.1.
Embodiment 1:
(1) scrapes the deinsectization streptomycete lawn of getting on the slant medium with inoculating needle, be inoculated into shake-flask seed substratum (first order seed substratum), under 28 ℃ of temperature, shaking speed 250r/min condition, cultivated 35 hours;
(2) seed liquor culture transferring to the secondary seed medium that obtains of step (1) (15L jar, the general 8 liters of seed culture mediums in sterilization back), inoculum size is 3-5ml, 28 ℃ of temperature, 200 rev/mins of rotating speeds, pressure 0.05MPa, ventilating ratio are under the 0.5vvm, cultivate 36 hours;
(3) secondary seed culture transferring to the fermentor tank (50L) that step (2) is obtained carries out fermentation culture, and the culture transferring amount is the 8%-10% of fermentation cylinder for fermentation substratum, i.e. the 50L jar; Sterilization post-fermentation and culture base is about 33L, probably is 36 liters after moving, and leavening temperature is 28 ℃; The real-time OUR value in the monitoring fermenting process tail gas in the fermenting process, after fermenting by 144 hours, promptly OUR decline occurs being about to but under the unconspicuous situation; Carry out gradient current according to the OUR value and add benefit sugar, benefit sugar employing concentration is 20% glucose solution, mends sugared speed control at 12-24ml/h; Be specially fermentation time 144-168 hour, and mended sugared speed 12ml/h; Fermentation time 169-193 hour, mend sugared speed 16ml/h; Fermentation time 194-218 hour, mend sugared speed 20ml/h; Fermentation time 219-243 hour, mend sugared speed 24ml/h, make at last that the OUR value is controlled at 11mmol/Lh in the fermented liquid, the continued fermentation was to putting jar in 243 hours;
(4) fermentation was carried out titration after 13 days.Warp analysis Avrmectin is tired and is 4832u/ml, and the fermentation titer of not mending sugar is 4056u/ml, tires and has improved 19.13%.
Embodiment 2:
Benefit sugar employing concentration is 30% glucose solution, and mend sugared speed and adopt: fermented 144-168 hour: mending sugared speed is 8ml/h; 169-193 hour, mending sugared speed was 13ml/h; 194-218 hour, mending sugared speed was 16ml/h, and 219-243 hour, mending sugared speed was 12ml/h.Other processing condition are all identical with embodiment 1 with step, and the Avrmectin that obtains is at last tired and is 4766u/ml, and the fermentation titer of not mending sugar is 4056u/ml, tires and has improved 17.50%.
Embodiment 3:
Benefit sugar employing concentration is 40% glucose solution, and mend sugared speed and adopt: fermented 144-168 hour: mending sugared speed is 8ml/h; 169-193 hour, mending sugared speed was 10ml/h; 194-218 hour, mending sugared speed was 12ml/h, and 219-243 hour, mending sugared speed was 8ml/h.Other processing condition are all identical with embodiment 1 with step, and the Avrmectin that obtains is at last tired and is 4936u/ml, and the fermentation titer of not mending sugar is 4056u/ml, tires and has improved 21.70%.
Embodiment 4:
Benefit sugar employing concentration is 10% glucose solution, and mend sugared speed and adopt: fermented 144-168 hour: mending sugared speed is 7ml/h; 169-193 hour, mending sugared speed was 17ml/h; 194-218 hour, mending sugared speed was 24ml/h, and 219-243 hour, mending sugared speed was 27ml/h.Other processing condition are all identical with embodiment 1 with step, and the Avrmectin that obtains is at last tired and is 4936u/ml, and the fermentation titer of not mending sugar is 4056u/ml, tires and has improved 21.70%.
Embodiment 5:
Benefit sugar employing concentration is 30% glucose solution, and mend sugared speed and adopt: fermented 144-168 hour: mending sugared speed is 13ml/h; 169-193 hour, mending sugared speed was 15ml/h; 194-218 hour, mending sugared speed was 10ml/h, and 219-243 hour, mending sugared speed was 7ml/h.Other processing condition are all identical with embodiment 1 with step, and the Avrmectin that obtains is at last tired and is 490lu/ml, and the fermentation titer of not mending sugar is 4056u/ml, tires and has improved 20.83%.
Experimental example:
1.1 Changing Pattern such as Fig. 1 of Fermentation Process of Parameter such as 50L fermenting process total reducing sugar, reducing sugar:
Fig. 1 provides reference frame for mending the sugar test in experiment, how the biochemical indicator of promptly mending sugar changes, and with the experiment of mending after the sugar what difference is arranged.Whether can provide the sugar opportunity of mending, fermenting process normal to a certain extent, Changing Pattern during the fermentation such as pH etc. are the bases that a series of experiments are carried out in the back.Fig. 2 is for mending sugared speed and thalline aging degree and the Avrmectin graph of a relation between tiring.From Fig. 2, can draw the opportunity of mending sugar.
1.2 confirming of sugared mode mended in 50L fermentation pilot scale
Feeding medium during fermentation has multiple in theory, and we have selected following three kinds of feed supplement modes to study in the experimentation: according to the total reducing sugar wear rate of every day, mend corresponding consumption sugar.
(1) disposable feed supplement mode intermittently: divides and mend for 3 times, benefit was gone into a septum secundum one day.
(2) flow feeding mode at the uniform velocity: add Glucose Liquid with mode at the uniform velocity.
(3) gradient flow feeding mode: divide 3 gradients, the feed rate gradient increases to initial rate 1/3rd.
These 3 kinds of feed supplement modes are mended the sugar operation, its result such as following table: from table 1, can find out, serve as to mend sugared opportunity to ferment 6 days; Fermentation period 290h; No matter take which kind of feed supplement mode, final Avrmectin is tired and all is improved to some extent, and wherein to add effect best for gradient current; Avrmectin is tired and is reached 4937ug/ml, and comparison is according to having improved 20.41%.
Three kinds of different feed supplement mode effects of table 1 relatively
1.3 fermenting several kinds, 50L mends sugared tactful comparative analysis
Mending sugared mode is that we have mainly analyzed following three kinds and have mended the sugar strategy on the experiment basis that adds of gradient current: for comparing, mend sugared modes for three kinds and all be chosen in 144h and mend the sugar operation.The result sees Fig. 3
(1) tactful based on the benefit sugar of total reducing sugar and reduced sugar wear rate
(2) tactful according to the benefit sugar of process pH
(3) tactful according to the benefit sugar of metabolizing parameters OUR
From the fermentation result, abamectin fermentedly carry out suitable benefit sugar in the middle and later periods and all can play to improve and tire, increase total hundred million and the effect that reduces production costs.Know from Fig. 3, after 144h mends sugar, finally adopt the third to mend sugared mode, promptly best based on the tactful effect of benefit sugar of metabolizing parameters OUR, tiring to reach 4976u/ml, and the relative comparison 4058u/ml that tires has improved 22.62%.
1.4 adopt on the scale 50L jar with OUR is that index is carried out Changing Pattern and output that gradient current adds the feeding glucose fermentation process parameter and increased substantially test
1.4.1 OUR parameter Changing Pattern in the conventional fermenting process of 50L jar
Before adopting OUR to mend sugared strategy, the OUR parameter Changing Pattern in the conventional fermenting process is followed the tracks of result such as Fig. 4.According to the data presentation of following the tracks of, the OUR peak appears at fermentation carries out about 12h, and subsequently, OUR has individual low ebb (relatively) about 40h, all analogue can occur at all batches.Further analysis can know that the 40h Avid kyowamycin is in the transformation point of elementary metabolism and secondary metabolism, produces element just behind the 40h and begins to start.After getting into secondary metabolism, OUR begins to stablize, and gets into stationary phase, but along with the carrying out of fermenting, nutritive substances such as substratum are consumed, and meta-bolites accumulates gradually, and bacterial metabolism weakens, and OUR is along with the carrying out of fermentation also progressively descends.Experiment shows that when fermenting near 200h, if do not mend the sugar operation, OUR possibly drop to below the 5mmol/Lh.
1.4.2 the 50L jar is the benefit sugar Changing Pattern of control foundation with OUR
In fermentation decreased later trend serious situation, proposing with OUR is the benefit sugar strategy of foundation to batch OUR that does not mend the sugar operation.Be to mend in the sugared process and do not mend batch compare of sugar according to fermentation with OUR, its result is as shown in Figure 5, mends sugared batch OUR at the later stage held stationary, and its value stabilization is about 10mmol/Lh.And do not mend sugar batch, its OUR descends behind 150h obviously, has reflected that thalline is old and feeble very fast, fermentation ends is more Zao than mending sugared batch.
1.4.3 with OUR is to mend the fermentation of sugar strategy on 2 tons of pilot scale jars to amplify checking
In order to verify the feasibility of mending the sugar strategy, on 2 tons of pilot scale jars, carried out the amplification confirmatory experiment, wherein the benefit sugar speed on 2 tons of jars adopts benefit sugar speed on the 50L jar to carry out simple geometric to amplify.Experimental result shows that this method can improve the fermentation unit of Avrmectin by a relatively large margin, amplifies for industrial production and has established scientific basic, and concrete experimental result is seen Fig. 6.Can know from Fig. 6, mend the sugar group and do not mend the sugar group and on OUR and final tiring, have than big difference.Mend the sugar group and tire and embody remarkable advantages, can reach 4982u/ml, improved 22.83% than the control group 4056u/ml that tires.Change from OUR, mending sugar opportunity is to begin about 144h, mends sugar group OUR downtrending and obviously eases up, and this is with to mend sugared speed relevant, and when OUR dropped near the 11mmol/Lh, the sugared speed of suitably control benefit can make the OUR value maintain 11mmol/Lh.And do not mend sugar group, in whole fermentation process, because of thalline old and feeble, hypopnea, the OUR fall is bigger than mending the sugar group far away, when the OUR that does not mend the sugar group drops to 8mmol/Lh when following, contrast is tired and is increased slowly, even increases.Contrast through mending sugar and not mending the sugar test at 2 tons of pilot scale jars; Suitably control the sugared speed of benefit according to OUR; Make fermentation level improve about 20%; For the technical scale fermentation level provides scientific basic, also verified simultaneously through adopting metabolizing parameters OUR fermentation to mend the feasibility that the sugar operation improves the Avrmectin production technique.
Claims (5)
1. produce Avrmectin technology based on metabolizing parameters OUR feeding glucose fermentation for one kind, it is characterized in that comprising following process step:
(1) the deinsectization streptomycete culture transferring is shaken to 250ml carries out first order seed in the bottle and cultivate;
(2) carrying out secondary seed in seed liquor culture transferring to the 15L seeding tank that step (1) is obtained cultivates;
(3) seed liquor culture transferring to the 50L fermentor tank that step (2) is obtained carries out fermentation culture, The real time measure fermentation tail gas OUR value in the fermenting process, and variation is adopted stream to add the sugared mode of benefit and is mended sugared the operation according to the OUR value; Mend the sugar operation after 144 hours in fermentation, it was the glucose solution of 20-40% that benefit sugar adopts concentration, fermentation 144-168 hour; Mending sugared speed is 7-13ml/h, and 169-193 hour, mending sugared speed was 10-17ml/h; 194-218 hour, mending sugared speed was 10-30ml/h, 219-243 hour; Mending sugared speed is 7-27ml/h, makes the OUR value be controlled at 10-13mmol/Lh.
2. as claimed in claim 1 a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that the first order seed culture condition is in the step (1): 28 ℃ of temperature; Under 250 rev/mins of the shaking speed; Cultivated 30-40 hour, the first order seed substratum that shakes in the bottle contains: W-Gum 28-32g/L, steeping water 3-7g/L, yeast extract paste 13-17g/L, KH
2PO
42-6g/L and zero(ppm) water, and accent PH is 7.0-7.2.
3. as claimed in claim 1 a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that the secondary seed culture condition is in the step (2): 28 ℃ of temperature; 200 rev/mins of rotating speeds, pressure 0.05MPa, ventilating ratio are under the 0.5vvm; Cultivated 36-48 hour, secondary seed medium contains in the seeding tank: W-Gum 28-32g/L, steeping water 3-7g/L, yeast extract paste 13-17g/L, KH
2PO
42-6g/L and zero(ppm) water, and accent PH is 7.0-7.2.
4. as claimed in claim 1 a kind of based on metabolizing parameters OUR feeding glucose fermentation production Avrmectin technology; It is characterized in that fermentation culture conditions is in the step (3): under 28 ℃ of temperature; Cultivated 13 days, the fermentation cylinder for fermentation substratum contains: W-Gum 110-130g/L, yeast powder 13-17g/L, bean cake powder 3-7g/L, groundnut meal 3-7g/L, KH
2PO
43-7g/L and zero(ppm) water, and accent pH is 7.0-7.2.
5. as claimed in claim 1ly a kind ofly produce Avrmectin technology, it is characterized in that in the step (3) that fermentation 144-168 hour, mending sugared speed was 8-12ml/h based on metabolizing parameters OUR feeding glucose fermentation; 169-193 hour; Mending sugared speed is 10-16ml/h, and 194-218 hour, mending sugared speed was 12-30ml/h; 219-243 hour, mending sugared speed was 8-24ml/h.
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Families Citing this family (8)
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| CN101979648B (en) * | 2010-09-10 | 2012-10-03 | 浙江升华拜克生物股份有限公司 | Method for producing avermectin by utilizing fermentation wastewater and carbohydrate supplement process |
| CN102703540B (en) * | 2012-05-25 | 2014-01-01 | 浙江升华拜克生物股份有限公司 | Process for producing salinomycin by glucose supplement and fermentation based on metabolic parameter OUR (oxygen uptake rate) |
| CN103642865B (en) * | 2013-11-18 | 2015-09-30 | 宁夏泰瑞制药股份有限公司 | A kind of A Foman streptomycete fermentation produces substratum and the fermentation process of ivermectin |
| CN105586374B (en) * | 2014-10-22 | 2019-06-18 | 重庆乾泰生物医药有限公司 | A method of sugar production doractin is mended based on metabolizing parameters reduced sugar |
| CN106755213B (en) * | 2016-12-23 | 2020-06-19 | 武汉科诺生物科技股份有限公司 | Validamycin fermentation process |
| CN108060193B (en) * | 2018-01-31 | 2021-08-10 | 天俱时工程科技集团有限公司 | Production process of abamectin |
| CN110551783B (en) * | 2019-09-23 | 2021-07-06 | 华东理工大学青岛创新研究院 | Fermentation method for producing gentamicin by using continuous flow feeding material with oxygen consumption rate as key control parameter |
| CN112029750A (en) * | 2020-06-10 | 2020-12-04 | 华东理工大学 | OUR-based fed-batch fermentation method for producing medium-temperature alpha-amylase by using bacillus subtilis |
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