CN1183474A - Process for producing L-lysine by fermentation - Google Patents

Process for producing L-lysine by fermentation Download PDF

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Publication number
CN1183474A
CN1183474A CN 97112748 CN97112748A CN1183474A CN 1183474 A CN1183474 A CN 1183474A CN 97112748 CN97112748 CN 97112748 CN 97112748 A CN97112748 A CN 97112748A CN 1183474 A CN1183474 A CN 1183474A
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Prior art keywords
grams per
substratum
methionin
litre
per liter
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CN 97112748
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CN1117869C (en
Inventor
中村尚志
仲山达哉
小山洋介
岛崎敬士
三轮治文
鹤田稔
田村光司
户坂修
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Ajinomoto Co Inc
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Ajinomoto Co Inc
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Priority claimed from JP12699291A external-priority patent/JP3074781B2/en
Priority claimed from JP27793891A external-priority patent/JP2932791B2/en
Application filed by Ajinomoto Co Inc filed Critical Ajinomoto Co Inc
Publication of CN1183474A publication Critical patent/CN1183474A/en
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/26—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control

Abstract

The present invention relates to a method for producing L-lysine by fermentation with an enhanced productivity, higher concentrations of the accumulated product and increased L-lysine yields.

Description

The method of fermentation production of L-lysine
The application is that application number is 92101496.1, the applying date is on March 9th, 1992, denomination of invention is divided an application for the application for a patent for invention of " method and apparatus of control carbon source concentration in aerobic cultivation of microorganism ".
The present invention relates to a kind of method of fermentation production of L-lysine.Because L-Methionin is under-supply in feed grains, so L-Methionin is a kind of important amino acid as broiler fodder or pig feed addictive use.
The present invention relates to a kind of method of fermentation production of L-lysine.The certain methods that forefathers described comprises, cultivates the microorganism that can produce L-Methionin with batch process or continuous processing, accumulation L-Methionin in substratum, and collect L-Methionin product.
Under the situation of batch treatment, the liquid nutrient medium that will contain carbon source and nitrogenous source places fermentor tank to carry out batch culture.Another kind method is to carry out adding continuously or off and on when culture feeds in raw material the substratum that only contains carbon source.
Under processed continuously situation, when cultivating substratum is infeeded in the fermentor tank continuously, and emit the nutrient solution of equal volume continuously, so that maintenance such as cell quantity or production concentration is constant.
When carrying out the L-fermenting lysine,, be difficult to reach high productivity though the accumulation volume of product or yield are high in the nutrient solution with conventional batch process.On the other hand, when adopting conventional continuous processing,, be difficult to reach high product accumulation volume or high yield though productivity is high.In order to adapt to L-Methionin growth of requirement and to produce L-Methionin with cheaper cost, must improve the productivity of L-fermenting lysine, improve product accumulated concentrations and yield.
Therefore, the fermentation method that need provide a kind of usefulness can solve the prior art technical barrier is produced the method for L-Methionin.The invention provides a kind of new fermentation process, thereby conventional batch treatment and processed continuously advantages are got up with high productivity, high product accumulated concentrations and high produced in yields L-Methionin.
An object of the present invention is to provide improving one's methods of a kind of fermentation production of L-lysine.
Another embodiment of the invention relates to a kind of method of fermentation production of L-lysine, and this method comprises: a kind of microorganism that can produce L-Methionin of inoculation in the liquid medium within; Cultivate this microorganism, and after the logarithmic phase of this microorganism, add the substratum that another batch contains carbon source simultaneously and have the nutrient of growth-promoting effect, be no more than 5 grams per liters with the carbon source concentration of keeping in the substratum; Collect the L-Methionin that produces and accumulate in the substratum.
From following detailed Description Of The Invention part, can obviously find out various other purposes of the present invention and advantage.
The present invention relates to produce the method for bacterium fermentation production of L-lysine with L-Methionin.L-Methionin production method provided by the present invention combines the advantage of conventional continuous fermentation method and conventional batchwise, that is: productivity height, product accumulated concentrations height, L-Methionin yield height.The applicant finds that the above-mentioned improvement of L-Methionin production method can realize in order to following method: inoculation can produce the microorganism of L-Methionin in the liquid medium within; Cultivate this microorganism, and add the fed-batch medium that contains carbon source simultaneously and have the nutrient of growth-promoting effect, be no more than 5 grams per liters to keep the carbon source concentration in the nutrient solution at the logarithmic growth after date of this microorganism; Collect the L-Methionin that produces and accumulate in the nutrient solution.
Therefore, the present invention relates to a kind of method of fermentation production of L-lysine, this method comprises: inoculation can produce the microorganism of L-Methionin in the liquid medium within; Cultivate this microorganism, and after the logarithmic phase of this microorganism, add the fed-batch medium that contains carbon source simultaneously and have the nutrient of growth-promoting effect, keep the carbon source concentration in the nutrient solution to be no more than 5 grams per liters simultaneously; Collect the L-Methionin that produces and accumulate in the nutrient solution.
In the method for the invention, the microorganism that can produce Methionin among the present invention is not had particular restriction, only require that this microorganism can produce L-Methionin.The example of this quasi-microorganism comprises the microorganism that belongs to brevibacterium sp (Brevibacterium) or Corynebacterium (Corynebacterium), and these microorganisms have makes its essential attributes with L-lysine production ability (homoserine auxotroph, S-(2-aminoethyl)-L-halfcystine resistance, α-chlorine hexanolactam resistance etc.).More particularly, the example of these microorganisms comprises Brevibacterium lactofermentus (Brevibacterium lactofermentum) CCTCC M90006, M90007; Brevibacterium flavum (Brevibacterium flavum) ATCC 21475; Corynebacterium acctoacidophlum (Corynebacterium acetoacidophilum) CCTCC M90008, M90009.
Liquid nutrient medium is not had particular restriction yet, but can use known completely liq substratum, wherein contain organic and inorganic nutrients source, for example carbon source, nitrogenous source and other micro-nutrients.
As carbon source used in the feed liquid of the present invention, can use any carbohydrate, organic acid, alcohols and other materials that are commonly used for fermentation raw material (carbon source), only require that above-mentioned Methionin production bacterium can absorb these carbon sources.
Nutrient with growth-promoting effect is meant amino acid, VITAMIN that can promote L-Methionin production bacteria growing and the crude substance that contains these compositions.Concrete example comprises soybean protein hydrolysate, pure female extract and corn steep liquor etc.
Just as known in the art, the fed-batch medium in the feeding culture generally only contains carbon source, and the liquid nutrient medium in the continuous processing then is completely.In the methods of the invention, fed-batch medium had both contained carbon source and had also contained the nutrient with growth-promoting effect.Using this fed-batch medium is one of feature of the inventive method.
In the method for the invention, the adding of substratum is to finish in the logarithmic growth process or logarithmic growth carries out after finishing in microorganism.Should avoid reinforced before logarithmic growth is finished, because the initial growth of bacterium is suppressed.
For in the logarithmic growth complete process or logarithmic growth add substratum after finishing, reinforced process both can carry out also can intermittently carrying out continuously.In addition, if the volume of substratum will be allowed the volume of adding above this fermentor tank in the expectation fermentor tank, then from fermentor tank, emit a part of nutrient solution in advance, emit a part of nutrient solution when allowing volume reinforced process can be proceeded thereby perhaps reach at volume.
So, importantly concerning the adding of substratum be exactly the concentration of carbon source is remained be no more than 5 grams per liters.This also is one of feature of the present invention.For making carbon source concentration keep this steady state value, the direct analysis carbon source concentration of can from nutrient solution, taking a sample frequently.In addition, also can measure pH or dissolved oxygen concentration,, just can control the adding of substratum by the deficiency of the variation monitoring carbon source of pH or dissolved oxygen concentration.Remain on 5 grams per liters or lower unless carbon source concentration is constant, otherwise growth of bacterium or the speed that generates L-Methionin will descend, this situation and purpose of the present invention do not match.
Feature of the present invention as mentioned above, other conditions such as fermentation condition then do not have particular restriction.For example, the temperature of fermentation production of L-lysine according to the present invention can be that used Methionin is produced any temperature that bacterium can grow, generally 25-45 ℃ scope, and preferred 30-40 ℃.The pH of fermenting process defined is generally in the scope of 5.8-8.5, preferred 6.5-7.5.For the adjusting of pH, can adopt inorganic or organic acidity or alkaline matter, and urea, lime carbonate or ammonia etc.
As fermentor tank used in the present invention, so long as amino acid fermentation fermentor tank commonly used can be taked Any shape.For example, can adopt complete mixing tank or the air band lift-type fermentor tank that the turbine type impeller is housed.
After culturing process is finished, can from fermented liquid, collect L-Methionin with ordinary method, for example spent ion exchange resin method, crystallization process and additive method, or with the combination of these methods.
Provide the following example and be in order to further specify the present invention, but should not think restrictive.
Embodiment
Embodiment 1
At three volumes respectively is shaking in the bottle of 500 milliliters, is respectively charged into 20 milliliters of substratum, contains 30 grams per liter glucose, 10 grams per liter ammonium chlorides, 3 grams per liter ureas, 1 grams per liter KH in this substratum 2PO 4, 100 mg/litre MgSO 47H 2O, 10 mg/litre FeSO 47H 2O, 8 mg/litre MnSO 44H 2O, 1 grams per liter (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 115 ℃ of heat sterilizations after 10 minutes, get the Brevibacterium lactofermentus FERM BP2294 (CCTCC M90006) that a platinum loop was cultivated 48 hours in advance from the meat soup inclined-plane, be seeded on the above-mentioned substratum, then in 31.5 ℃ of following shake-flask culture 24 hours.Above-mentioned steps is used for seed culture.
In three volumes are 1 liter small-sized fermentation jar, be respectively charged into 300 milliliters of substratum (pH7.0) in every jar, contain 80 grams per liter molasses (in sugared content), 50 grams per liter ammonium sulfate, 1 grams per liter KH in this substratum 2PO 4, 1 grams per liter MgSO 47H 2O, 100 mg/litre (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 120 ℃ of following heat sterilizations 15 minutes.After being cooled to 31.5 ℃, add the above-mentioned substratum that carried out shake-flask culture in each fermentor tank, add-on is 15 milliliters of each fermentor tanks.Cultivate under following condition: temperature is 31.5 ℃; Air velocity is 0.5vvm; Mixing speed is 700 rev/mins.
Three fermentor tanks one of them, the sugar in substratum stops to cultivate (conventional batch culture) when using up, with the concentration of the L-Methionin that accumulates in the acid copper ninhydrin colorimetry quantitative assay substratum.In other two fermentor tanks, the sugared concentration in substratum becomes 5 grams per liters or begins to add fed-batch medium when lower.In fermentor tank, fed-batch medium only contains glucose (40 grams per liter) (conventional feeding culture) therein; In fermentor tank of the present invention, fed-batch medium contains glucose (40 grams per liter), soybean protein hydrolysate (100 mg/litre are in nitrogen content), vitamin (0.1 mg/litre) and vitamin H (0.3 mg/litre).When cultivating in these fermentor tanks, control fed-batch medium feed rate is so that the sugared concentration in the nutrient solution remains on 5 grams per liters or lower.After in each culture, adding 100 milliliters of fed-batch mediums, when using up, finishes the sugar in nutrient solution cultivation.The concentration of the L-Methionin that accumulates in the quantitative assay nutrient solution.
Cultivation results in these three fermentor tanks is shown in table 1.
Table 1 fermentation process L-Methionin productivity L-Methionin yield
(grams per liter hour) (%) batch culture (prior art) 1.9 26 feeding culture (prior art) 2.1 27 the present invention 2.6 30
As seen from Table 1, the productivity of L-Methionin and yield are all fine.
Embodiment 2
At two volumes respectively is 500 milliliters shaking in the bottle, is respectively charged into 20 milliliters of substratum, contains 30 grams per liter glucose, 10 grams per liter ammonium chlorides, 3 grams per liter ureas, 1 grams per liter KH in this substratum 2PO 4, 100 mg/litre MgSO 47H 2O, 10 mg/litre FeSO 47H 2OO, 8 mg/litre MnSO 44H 2O, 100 mg/litre (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 115 ℃ of heat sterilizations after 10 minutes, get the Brevibacterium lactofermentus FERM BP2297 (CCTCC M90007) that a platinum loop was cultivated 48 hours in advance from the meat soup inclined-plane, be seeded on the above-mentioned substratum, then in 31.5 ℃ of following shake-flask culture 24 hours.Above-mentioned steps is used for seed culture.
In two volumes are 1 liter small-sized fermentation jar, be respectively charged into 300 milliliters of substratum (pH 7.0) in every jar, contain 80 grams per liter molasses (in sugared content), 50 grams per liter ammonium sulfate, 1 grams per liter KH in this substratum 2PO 4, 1 grams per liter MgSO 47H 2O, 100 mg/litre (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 120 ℃ of following heat sterilizations 15 minutes.After being cooled to 31.5 ℃, add the above-mentioned substratum that carried out shake-flask culture in each fermentor tank, add-on is 15 milliliters of each fermentor tanks.Cultivate under following condition: temperature is 31.5 ℃; Air velocity is 0.5vvm, and mixing speed is 700 rev/mins.
Sugared concentration in nutrient solution becomes 5 grams per liters or begins to add fed-batch medium when lower.Contain glucose (40 grams per liter), soybean protein hydrolysate (100 mg/litre are in nitrogen content), vitamin (0.1 mg/litre) and vitamin H (0.3 mg/litre) in this fed-batch medium.In fermentor tank, the feed rate of control fed-batch medium in cultured continuously is so that the sugared constant concentration in the nutrient solution remains on 5 grams per liters or lower (the present invention) therein.In another fermentor tank, the feed rate during cultured continuously will make sugared concentration be in the scope interior (contrast) of 5-15 grams per liter.After in each culture, adding 100 milliliters of fed-batch mediums, when using up, finishes the sugar in nutrient solution cultivation.The concentration of the L-Methionin that accumulates in the quantitative assay nutrient solution.
Cultivation results in these two fermentor tanks is shown in table 2.
The control of the sugared concentration of table 2 (grams per liter) L-Methionin productivity L-Methionin yield
(grams per liter hour) (%) is lower than 5 (the present invention), 3.5 41 5-15 (contrast) 2.9 38
Embodiment 3
At three volumes respectively is 500 milliliters shaking in the bottle, is respectively charged into 20 milliliters of substratum, contains 30 grams per liter glucose, 10 grams per liter ammonium chlorides, 3 grams per liter ureas, 1 grams per liter KH in this substratum 2PO 4, 100 mg/litre MgSO 47H 2O, 10 mg/litre FeSO 47H 2O, 8 mg/litre MnSO 44H 2O, 1 grams per liter (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 115 ℃ of heat sterilizations after 10 minutes, get from the meat soup inclined-plane platinum loop preliminary election cultivate 48 hours have a liking for acetyl-acetate rod bacillus FERM BP2295 (CCTCC M90008), be seeded on the above-mentioned substratum, then in 31.5 ℃ of following shake-flask culture 24 hours.Above-mentioned steps is used for seed culture.
In three volumes are 1 liter small-sized fermentation jar, be respectively charged into 300 milliliters of substratum (pH 7.0) in every jar, contain 80 grams per liter molasses (in sugared content), 50 grams per liter ammonium sulfate, 1 grams per liter KH in this substratum 2PO 4, 1 grams per liter MgSO 47H 2O, 100 mg/litre (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 120 ℃ of following heat sterilizations 15 minutes.After being cooled to 31.5 ℃, add the above-mentioned substratum (seed culture medium) that carried out shake-flask culture in each fermentor tank, add-on is 15 milliliters of each fermentor tanks.Cultivate under following condition: temperature is 31.5 ℃; Air velocity is 0.5vvm, and mixing speed is 700 rev/mins.
Sugared concentration in nutrient solution becomes 5 grams per liters or when lower, begins to add fed-batch medium.Fed-batch medium of the present invention contains glucose (40 grams per liter), soybean protein hydrolysate (100 mg/litre are in nitrogen content), vitamin (0.1 mg/litre) and vitamin H (0.3 mg/litre).The feed rate of control fed-batch medium when cultivating is so that the sugared constant concentration in the substratum remains on 5 grams per liters or lower.After in culture, adding 100 milliliters of fed-batch mediums, when using up, the sugar in nutrient solution from fermentor tank, emits 100 milliliters of substratum.
When proceeding to cultivate, further add fed-batch medium.Still stipulate the sugared concentration in the substratum in this case, make it remain on 5 grams per liters or lower.After adding 100 milliliters of fed-batch mediums, the sugar in nutrient solution stops when using up cultivating.The substratum in the fermentor tank and the substratum of emitting are previously merged the concentration of the L-Methionin that quantitative assay wherein accumulates.
The result shows, the productivity of Methionin is 2.9 grams per liters hour, and the yield of Methionin is 28%.
Embodiment 4
At two volumes respectively is 500 milliliters shaking in the bottle, is respectively charged into 20 milliliters of substratum, contains 30 grams per liter glucose, 10 grams per liter ammonium chlorides, 3 grams per liter ureas, 1 grams per liter KH in this substratum 2PO 4, 100 mg/litre MgSO 47H 2O, 10 mg/litre FeSO 47H 2O, 8 mg/litre MnSO 44H 2O, 1 grams per liter (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 115 ℃ of following heat sterilizations after 10 minutes, get the Corynebacterium acctoacidophlum FERM BP2296 (CCTCC M90009) that a platinum loop was cultivated 48 hours in advance from the meat soup inclined-plane, be seeded on the above-mentioned substratum, then in 31.5 ℃ of following shake-flask culture 24 hours.Above-mentioned steps is used for seed culture.
In two volumes are 1 liter small-sized fermentation jar, be respectively charged into 300 milliliters of substratum (pH 7.0) in every jar, contain 80 grams per liter molasses (in sugared content), 50 grams per liter ammonium sulfate, 1 grams per liter KH in this substratum 2PO 4, 1 grams per liter MgSO 47H 2O, 100 mg/litre (in nitrogen content) soybean protein acid hydrolysate, 0.1 mg/litre vitamin, 0.3 mg/litre vitamin H.Should cultivate based on 120 ℃ of following heat sterilizations 15 minutes.After being cooled to 31.5 ℃, add the above-mentioned substratum that carried out shake-flask culture in each fermentor tank, add-on is 15 milliliters of each fermentor tanks.Cultivate under following condition: temperature is 31.5 ℃; Air velocity is 0.5vvm, and mixing speed is 700 rev/mins.
Therein in fermentor tank, the sugared concentration in nutrient solution becomes 5 grams per liters or when lower, begins to add fed-batch medium.This fed-batch medium contains glucose (40 grams per liter), soybean protein hydrolysate (100 mg/litre are in nitrogen content), vitamin (0.1 mg/litre), vitamin H (0.3 mg/litre) (the present invention).The feed rate of control fed-batch medium when proceeding to cultivate is so that the sugared constant concentration in the nutrient solution remains on 5 grams per liters or lower.After adding 100 milliliters of fed-batch mediums, when using up, the sugar in nutrient solution from fermentor tank, emits 100 milliliters of nutrient solutions.
When proceeding to cultivate, further add fed-batch medium.Still stipulate the sugared concentration in the substratum in this case, make it remain on 5 grams per liters or lower.After adding 100 milliliters of fed-batch mediums, the sugar in nutrient solution stops when using up cultivating.The nutrient solution in the fermentor tank and the nutrient solution of emitting are previously merged the concentration of the L-Methionin that quantitative assay wherein accumulates.
The result shows, the productivity of Methionin is 3.6 grams per liters hour, and the yield of Methionin is 38%.
Another fermentor tank begins to add the fed-batch medium of using for cultured continuously in the cultivation beginning after 25 hours.The substratum that uses as fed-batch medium obtains 4 times of initial medium dilutions.Feed about 1 up-flow with 0.05 extension rate per hour and add substratum to carry out cultured continuously.After reaching permanent attitude, the concentration of L-Methionin in the quantitative assay substratum.
The result shows, the productivity of Methionin is 3.4 grams per liters hour, and the yield of Methionin is 28%.
As indicated in embodiment 1-4, the present invention can be with the high productivity fermentation production of L-lysine of conventional continuous processing, the high product accumulated concentrations and the high yield that have kept conventional batch process fermentation to be reached simultaneously.Therefore, utilize the present invention that the productivity of suitability for industrialized production L-Methionin is improved greatly, and cost reduce.
Above-mentioned all publications are all classified reference as at this.
More than for clear and be convenient to understand for the purpose of slightly described the present invention in detail, but this area professional will appreciate that by reading the disclosure, can make various changes and not depart from essential scope of the present invention its form and details.

Claims (1)

1. the method for a fermentation production of L-lysine, this method comprises the steps:
(i) a kind of microorganism that can produce L-Methionin of inoculation in the liquid medium within;
(ii) cultivate described microorganism, and after the logarithmic phase of described microorganism, add the substratum that another batch contains carbon source simultaneously and have the nutrient of growth-promoting effect, the concentration of wherein said carbon source in substratum keeps being no more than 5 grams per liters;
(iii) collect the L-Methionin that produces and accumulate in the substratum.
CN97112748A 1991-03-12 1997-06-10 Process for producing L-lysine by fermentation Expired - Lifetime CN1117869C (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP126992/1991 1991-03-12
JP12699291A JP3074781B2 (en) 1991-03-12 1991-03-12 Production method of L-lysine by fermentation method
JP126992/91 1991-03-12
JP277938/91 1991-10-24
JP27793891A JP2932791B2 (en) 1990-11-30 1991-10-24 Method and apparatus for controlling carbon source concentration in microbial aerobic culture
JP277938/1991 1991-10-24

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CN92101496A Division CN1041534C (en) 1991-03-12 1992-03-09 Method and apparatus for controlling carbon source concentration in aerobic cultivation of microorganism

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CN1117869C CN1117869C (en) 2003-08-13

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CN108660168A (en) * 2017-03-27 2018-10-16 上海医药工业研究院 A kind of zymotechnique improving L-Trp yield

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CN1064404C (en) * 1996-09-19 2001-04-11 中国科学院化工冶金研究所 Cultivation method by controlling rhythm of somatic metabolism during the process of aerobe bacteria fermentation
US20170017891A1 (en) * 2014-01-30 2017-01-19 Valitacell Limited A method of predicting relative fed batch production titer of a panel of clonally-derived producer cells
CN106222309A (en) * 2016-07-28 2016-12-14 山东金朗生物科技有限公司 A kind of fermentable produces the control of additive raw material method improving L alanine yield
CN111099740B (en) * 2018-10-26 2022-06-07 中国石油化工股份有限公司 Feed supplement control method for chemoautotrophic microorganism culture process
CN116855370A (en) * 2023-07-19 2023-10-10 安及义实业（上海）有限公司 Automatic feeding device and method for bioreactor or fermentation tank

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US3926738A (en) * 1972-05-10 1975-12-16 Wilson John D Method and apparatus for control of biochemical processes
US4680267A (en) * 1985-03-01 1987-07-14 New Brunswick Scientific Company, Inc. Fermentor control system
JP2817172B2 (en) * 1989-03-07 1998-10-27 味の素株式会社 Production of L-lysine by fermentation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108660168A (en) * 2017-03-27 2018-10-16 上海医药工业研究院 A kind of zymotechnique improving L-Trp yield

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