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    • 3. 发明授权
    • Method and apparatus for controlling carbon source concentration in
aerobic cultivation of a microorganism
    • 用于控制微生物需氧培养中碳源浓度的方法和装置
    • US5912113A
    • 1999-06-15
    • US905713
    • 1997-08-04
    • Takashi NakamuraTatsuya NakayamaYosuke KoyamaKeishi ShimazakiHarufumi MiwaMinoru TsurutaKoji TamuraOsamu Tosaka
    • Takashi NakamuraTatsuya NakayamaYosuke KoyamaKeishi ShimazakiHarufumi MiwaMinoru TsurutaKoji TamuraOsamu Tosaka
    • C12M1/36C12N1/20C12P1/00C12P13/06C12P13/08C12Q3/00C12N1/12C12N1/14
    • C12M41/32C12M41/26C12M41/34C12M41/48C12N1/20C12P13/08Y10S435/822Y10S435/948
    • The present invention is a method for aerobically cultivating yeast or bacteria in a culture medium of fed-batch, continuous or cell-recycling continuous cultures, wherein the carbon source concentration in the culture medium is maintained at a constant low level of under g/l. The carbon source concentration is maintained by measuring the carbon consumption of a culture of the yeast or bacteria in a preliminary experiment. The rate is determined between the time the culture is started and a time when the carbon source is exhausted. A feeding time is then determined wherein the activity of the yeast or bacteria in the presence of the carbon source does not change and a volume of the carbon source to be used in a first feeding (So) is set as So=.nu..times.T. Then, in a main culture, a first feeding of a volume of the carbon source (So) is added for the time (T), and the exhaustion of the carbon source is detected as an increase in pH or an increase in concentration of oxygen dissolved in the culture medium. A second feeding of a volume of the carbon source is then added for the time (T), and the feeding rate is determined based on a period (.tau.) before which the second feeding is added as follows:if 10 min..gtoreq..tau., the feeding rate of the feed solution is set at 1.1.times..nu.;if 30 min..gtoreq..tau.>10 min., the feeding rate of the feed solution is set at .nu.;if 60 min..gtoreq..tau.>30 min., the feeding rate is set at 0.9.times..nu.; orif 120 min..gtoreq..tau.>60 min., the feeding rate is set at 0.8.times..nu.. By modifying the feeding rate in this way, the carbon source concentration in the cultivation vessel is kept at the constant low level of under 5 g/l.
    • 本发明是在补料分批,连续或细胞循环连续培养的培养基中有氧培养酵母或细菌的方法,其中培养基中的碳源浓度保持在低于g / l的恒定低水平 。 通过在初步实验中测量酵母或细菌的培养物的碳消耗来维持碳源浓度。 速率是在文化开始时间和碳源耗尽时间之间确定的。 然后确定进料时间,其中在碳源存在下酵母或细菌的活性不变,并且在第一次进料(So)中使用的碳源的体积被设定为So = nu xT。 然后,在主培养中,在时间(T)下加入体积的碳源(So)的第一次进料,并且随着pH的增加或氧浓度的增加检测碳源的耗尽 溶解在培养基中。 然后在时间(T)下加入体积的碳源的第二次进料,并且基于如下加入第二次进料的时间段(τ)确定进料速率:如果10分钟> / = tau,进料溶液的进料速率设定为1.1×nu; 如果30分钟,则进料溶液的进料速度设定为nu; 如果60分钟> 30分钟,进料速率设定为0.9x nu; 或者如果120分钟,则进料速率设定为0.8x nu。 通过以这种方式改变进料速率,培养容器中的碳源浓度保持在5g / l以下的恒定低水平。