• Journal of Microbiology and Biotechnology
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• 제11권5호
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• pp.739-748
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• 2001

A self-organizing fuzzy logic controller using a genetic algorithm is described, which controlled the glucose concentration for the enhancement of flavonoid production in a fed-batch cultivation of Scutellaria baicalensis G. plant cells. The substrate feeding strategy in a fed-batch culture was to increase the flavonoid production by using the proposed kinetic model. For the two-stage culture, the substrate feeding strategy consisted of a first period with 28 g/I of glucose to promote cell growth, followed by a second period with 5 g/I of glucose to promote flavonoid production. A simple fuzzy logic controller and the self-organizing fuzzy logic controller using a genetic algorithm was constructed to control the glucose concentration in a fed-batch culture. The designed fuzzy logic controllers were applied to maintain the glucose concentration at given set-points of the two-stage culture in fed-batch cultivation. The experimental results showed that the self-organizing fuzzy logic controller improved the controller\`s performance, compared with that of the simple fuzzy logic controller. The specific production yield and productivity of flavonoids in the two-stage culture were higher than those in the batch culture.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2000년도 춘계학술발표대회
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• pp.271-274
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• 2000

A study was carried out to select a nitrogen source and the optimize the C/N ratio for the maximum cell growth of Phaffia rhodozyma in fed-batch culture. The yeast extract was the best organic nitrogen source. In the batch culture experiments, the highest cell yield was obtained 0.575 g-cell/g-glucose from 10 g/L and 10 g/L yeast extract. In the fed-batch experiments, the maximum cell concentration was obtained 33.1 g/L from the C/N ratio of 2:1 while the astaxanthin concentration of cell was Increased by increasing the C/N ratio, of feed medium.

• KSBB Journal
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• 제18권5호
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• pp.418-423
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• 2003

발효조의 냉각수 공급 제어 신호와 냉각수의 유출입 지점의 온도를 온라인으로 측정하여 이 값들로부터 냉각량을 추정할 수 있는 실험식을 얻었다. 회분식 배양을 통하여 냉각량이 온라인으로 측정될 수 있음을 확인하였고 기질의 재투입시 냉각량의 변화를 통하여 유가배양의 제어변수로 활용할 수 있음을 점검하였다. 미리 프로그램된 목표 냉각량의 증가곡선에 따라 냉각량이 증가되면서 세포가 자라도록 유가배양을 실시하였다. 본 연구를 통하여 냉각량의 온라인 측정방법을 제시하였고 이를 유가배양 제어변수로 활용하여 세포의 성장속도를 조절할 수 있음을 보였다.

• Journal of Microbiology and Biotechnology
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• 제13권2호
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• pp.175-181
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• 2003

The production of a carotenoid astaxanthin, a growth-associated principal pigment, is limited in a batch cultivation, because a high glucose concentration severely inhibits the cell growth and also influences the carotenoid production. Therefore, a fermentation strategy including effective chemicals for the high-level production of cells and astaxanthin by a mutant strain Phaffia rhodozyma AJ-6-1 was developed in a fed-batch culture. First, a production medium for maximizing the cell and astaxanthin yields was formulated and optimized. Using this optimized medium, the highest cell and astaxanthin concentrations obtained were about 38.25 g/1 and 34.77 mg/1, respectively. In addition, an attempt was made to increase the amount of astaxanthin using effective chemicals such as ethanol and acetic acid, which are known at an inducer and/or precursor of carotenoid synthesis. When either 10g/1 ethanol or 5 g/1 acetic acid was added to investigate the resulting astaxanthin content, a relatively high astaxanthin concentration or 45.62 mg/l and 43.87 mg/1, respectively, was obtained, and the cell concentrations also increased slightly under these conditions. Therefore, these results imply that a fed-batch culture of the mutant strain P. rhodozyma AJ-6-1 could be effectively employed in the commercial production of astaxanthin, although the factors affecting the productivity remain to be elucidated.

• Biotechnology and Bioprocess Engineering:BBE
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• 제4권1호
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• pp.21-25
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• 1999

Two low-salt complex media, bactopeptone and desalted yeast extract, were used for high density cultivation of the hyperthermophilic archaeon Sulfolobus solfataricus (DSM 1617). Bactopeptone, which has low mineral ion content among various complex media, was good for cell growth in batch cultures; the maximal cell density in bactopeptone was comparable to that in yeast extract. However, cell growth was rather poor when bactopeptone was added by the fed-batch procedure. Since several vitamins are deficient in abctopeptone, the effect of vitamins on cell growth was examined. Among the vitamins tested, pyridoxine was found to improve the growth rate of S. solfataricus. To reduce the growth inhibition caused by mineral ions, yeast extract was dialyzed against distilled water and then fed-batch cultures were carried out using a fed medium containing desalted yeast extract. Although the concentrations of mineral ions in yeast extract were significantly lowered by the dialysis whether low molecular weight solutes in yest extract are crucial for cell growth, we investigated the effect of trehalose, a most abundant compatible solute in yeast extract, on the growth pattern. Cell densities were increased and the length of the lag phase was markedly shortened by the presence of trehalose, indicating that trehalose plays an important role in the growth of S. solfataricus.

• Journal of Microbiology and Biotechnology
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• 제6권4호
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• pp.295-298
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• 1996

Under glutamine-limited condition, $2\times10^6$ (viable cells/ml) of maximum cell density and 13.5 ($\mu g$/ml) of tissue-type Plasminogen Activators (tPA) production were maintained by spike feeding fresh medium in fed-batch cultivation of human recombinant melanoma cells. It showed that tPA production was much seriously affected than cell growth according to initial glutamine concentrations. Above 3.4 (mmol/I) of glutamine concentration both cell growth and tPA production were not much affected by increasing initial glutamine concentration. Glutamine depleted situation was occurred at latter periods of batch and fed-batch cultivations below 5.4 (mmole/I) of initial glutamine concentration. It also showed that maximum glutamine consumption and ammonia evolution rates were closely related to initial glutamine concentrations. Maximum specific tPA production rate was estimated as $8.1\times19^{-6}$ ($\mu g$/cells/h) at 3.4(mmol/I) of glutamine concentration, which is higher than that from other batch and fed-batch processes.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.390-393
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• 2001

The optimal temperature, pH and aeration rate for spore production by Bacillus polyfermenticus SCD in 500 ml shake flask and 5-1 jar fermenter were found to be $32^{\circ}C$, 7.0 and 1.0 vvm. respectively. When batch culture processes was performed under optimized culture conditions. viable cells were $3.3{\times}10^{10}$ CFU/ml and spore cells were $3.3{\times}10^{10}$ CFU/ml. Fed-batch culture processes were also examined with regard to higer maximum viable cell and spore production. The highe viable cells and spores were obtained in 5-1 jar fermenter at 72 h cultivation time by strategy in an intermediate feeding mode with 60% glucose solution 150 ml and 5% soybean flour solution 150 ml fed to the fermenter twice, and the productivity of spore cells was significantly increased. Finally. volumetric productivity of spore cells on fed-batch culture indicated $9.9{\times}10^8$ CFU/ml/h, which was approximately 2 times higher than batch culture. Thus, fed-batch culture show a promise as an industrial production method.

• 생명과학회지
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• 제9권3호
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• pp.293-299
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• 1999

하이브리도마 세포 배양을 통한 단일 군항체 생산성을 향상시키기 위해서는 배양환경에 의해 유해 대사산물 생산이 어떤 식으로 변화되는가에 대한 이해가 필요하다 세포성장과 단일 군항체 생산을 저해시키는 대사물질 중에 하나인 젖산의 생성을 줄이기 위해, 포도당의 젖산으로의 전환율에 영향을 미치는 인자들에 대해 연구하였다. 초기 포도당 농도가 높을수록, 세포 성장이 빠를 수록 젖산으로의 전환율이 커짐을 알 수 있었다. 또한 세포농도에 따른 비성장속도 변화에 대한 모델식을 기초로 하여 포도당 소비속도만큼 포도당을 공급하는 유가배양을 통해 젖산 생성을 19% 감소시켰고, 적분세포 농도 증가를 통해 단일군항체 생산성을 41% 향상시킬 수있었다.

• Journal of Microbiology and Biotechnology
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• 제12권4호
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• pp.617-621
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• 2002

In order to optimize the carrot hairy root culture for SOD production, a fed-batch culture of hairy roots was performed in a bioreactor. Maximum SOD activity was obtained when the hairy roots were transferred to the MS medium containing 110 g/1 concentration of sucrose. By controlling the sucrose concentration (70 g/1 sucrose for growth and 110 g/1 sucrose far production, respectively) In a two-stage fed-batch culture, 29 g/1 of the hairy roots was obtained based on the final dry mass. The volumetrically determined SOD activity and productivity in the fed-batch culture were about 6 times higher than those from the flask culture containing sucrose at 30 g/1 concentration.

• KSBB Journal
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• 제13권4호
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• pp.456-460
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• 1998

Fed-batch fermentations were carried out in order to improve the efficiency of hirudin production by recombinant Saccharomyces cerevisiae. A fed-batch fermentation done with the optimized semi-synthetic medium resulted in a maximum hirudin concentration of 342mg/$\ell$ by keeping a galactose concentrations between 10 and 30g/$\ell$ which corresponded to a 11.4-fold increase in hirudin concentration compared with the simple bach fermentation done with the same medium. Comparison of the chromatographic pattern of proteins in the growth medium clearly showed that the use of the semi-synthetic medium is more advantageous for separation of hirudin than the case o fusing the complex medium. Continuous cell recycle fermentation done at dilution rate of 0.1h-1 and an inlet galactose concentration of 100g/$\ell$ yielded a maximum hirudin productivity of 19.1mg hirudin/$\ell$$.$h.