• Journal of Microbiology and Biotechnology
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• 제16권11호
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• pp.1690-1698
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• 2006

In order to investigate the effect of dissolved oxygen (DO) level on AVM $B_{1a}$ production by a high yielding mutant of Streptomyces avermitilis, five sets of bioreactor cultures were performed under variously controlled DO levels. Using an online computer control system, the agitation speed and aeration rate were automatically controlled in an adaptive manner, responding timely to the oxygen requirement of the producer microorganism. In the two cultures of DO limitation, the onset of AVM $B_{1a}$ biosynthesis was observed to casually coincide with the fermentation time when oxygen-limited conditions were overcome by the producing microorganism. In contrast, this phenomenon did not occur in the parallel fermentations with DO levels controlled at around 30% and 40% throughout the entire fermentation period, showing an almost growth-associated mode of AVM $B_{1a}$ production: AVM $B_{1a}$ biosynthesis under the environments of high DO levels started much earlier than the corresponding oxygen-limited cultures, leading to a significant enhancement of AVM $B_{1a}$ production during the exponential stage. Consequently, approximately 6-fold and 9-fold increases in the final AVM $B_{1a}$ production were obtained in 30% and 40% DO-controlled fermentations, respectively, especially when compared with the culture of severe DO limitation (the culture with 0% DO level during the exponential phase). The production yield ($Y_{p/x}$), volumetric production rate (Qp), and specific production rate (${\bar{q}}_p$) of the 40% DO-controlled culture were observed to be 14%, 15%, and 15% higher, respectively, than those of the parallel cultures that were performed under an excessive agitation speed (350 rpm) and aeration rate (1 vvm) to maintain sufficiently high DO levels throughout the entire fermentation period. These results suggest that high shear damage of the high-yielding strain due to an excessive agitation speed is the primary reason for the reduction of the AVM $B_{1a}$ biosynthetic capability of the producer. As for the cell growth, exponential growth patterns during the initial 3 days were observed in the fermentations of sufficient DO levels, whereas almost linear patterns of cell growth were observed in the other two cultures of DO limitation during the identical period, resulting in apparently lower amounts of DCW. These results led us to conclude that maintenance of optimum DO levels, but not too high to cause potential shear damage on the producer, was crucial not only for the cell growth, but also for the enhanced production of AVM $B_{1a}$ by the filamentous mycelial cells of Streptomyces avermitilis.

• KSBB Journal
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• 제18권2호
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• pp.155-160
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• 2003

Streptoverticillium morbaraene로부터 미생물 유래 transglutaminase 생산을 위하여 최적의 용존산소 농도를 구명하였다. 용존산소는 용존산소 농도 자동 조절 시스템에 의해 조절되었다. 발효 중 용존산소 농도 조절을 위하여 통기속도는 0.3-3.9 L/min, 교반속도는 260-360 rpm으로 각각 범위를 설정하였다. 용존산소 농도를 조절한 다양한 회분식 배양에서 용존산소가 20%일 때 최대 미생물유래 transgiutaminase 생산이 가능하였다. 최분배양에서 용존산소 농도를 20%로 조절한 경우 미생물유래 transglutaminase 생산은 2.12 U/mL이었고, 용존산소를 조절하지 않은 회분식 배양의 미생물유래 transglutaminase 생산보다 1.1배 향상되었다. 역시 가장 높은 미생물유래 transglutaminase 생산은 용존산소를 20%로 조절한 유가식 배양에서 가능하였으며, 용존산소를 조절하지 않은 회분식 배양의 미생물유래 transglutaminase 생산에 비교해서 1.3배 증가하였다. 최대 건조균체량과 미생물유래 transglutaminase 생산은 각각 13.2 g/L와 2.6 U/mL이었다. 용존산소를 20%로 용존산소 농도 자동 조절 시스템에 의해 조절한 유가식 배양은 미생물유래 transgiutaminase 생산에 적절하였으며 다른 미생물 배양에도 적용할 수 있을 것으로 판단된다.

• 대한환경공학회지
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• 제28권7호
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• pp.764-769
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• 2006

미생물을 접종하지 않은 동전기 공정에서 전기분해에 의한 양극조에서 산소의 발생은 전류밀도에 비례하였으며 전해질을 순환시킴에 따라 생물반응기내 전해질과 함께 용존산소농도가 증가하였다. 전류의 공급과 함께 미생물 농도는 급격히 증가하였으며 이때 미생물의 산소소비량이 증가되어 용존산소농도가 감소되었다. Pentadecane-오염토양에 대한 동전기 생물학적 복원의 결과에서 높은 전류밀도 1.88 $mA/cm^2$에서 비록 산소의 발생량은 많았지만 오히려 증가된 유기산이 전해질 pH와 미생물 활성을 감소시키므로 미생물 농도와 제거효율이 0.63 $mA/cm^2$보다 낮게 나타났다. 0.63 $mA/cm^2$에서 적절한 산소의 공급과 동시에 전해액 pH의 감소가 작았으므로 최적의 미생물 농도와 제거효율을 얻을 수 있었다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권2호
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• pp.130-135
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• 2000

The characteristics of two different modes of perfusion culture, intermittent and continuous bleedings, were investigated by culturing the hybridoma cells producing von Willebrand Factor (vWF) monoclonal antibody (McAb) in a 15 L bioreactor without clogging the filter. Both culture methods exhibited similar profiles of cell density and metabolite concentrations during the culture period at the cell concentration of around 1${\times}$107 cells/mL. When the perfusion rate was increased, the intermittrnt bleeding culture showed problems of ammonia accumulation and decrease of cell viability. The continuous bleeding culture in terms of nutrient consumption and metabolite production kinetics. But the analysis of specific oxygen consumption rate showed that the specific oxygen consumption rate of intermittent bleeding culture was similar to that of exponential growth phase. The continuous bleeding culture showed higher specific oxygen consumption rate of intermittent bleeding culture. finally we proved the possibility of long-term operation of continuous bleeding culture and produced approximately 40 g of vWF McAb in a 15L bioreactor after one-month operation.

• Journal of Microbiology and Biotechnology
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• 제23권10호
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• pp.1445-1453
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• 2013

The scale-up criterion of constant oxygen mass transfer coefficient ($k_La$) was applied for the production of itaconic acid (IA) in a 50 L pilot-scale fermentor by the fungal cells of Aspergillus terreus. Various operating conditions were examined to collect as many $k_La$ data as possible by adjusting the stirring speed and aeration rate in both 5 L and 50 L fermentor systems. In the fermentations performed with the 5 L fermentor, the highest IA production was obtained under the operating conditions of 200 rpm and 1.5 vvm. Accordingly, we intended to find out parallel agitation and aeration rates in the 50 L fermentor system, under which the $k_La$ value measured was almost identical to that ($0.02sec^{-1}$) of the 5 L system. The conditions of 180 rpm and 0.5 vvm in the 50 L system turned out to be optimal for providing almost the same volumetric amount of dissolved oxygen (DO) into the fermentor, without causing shear damage to the producing cells due to excessive agitation. Practically identical fermentation physiologies were observed in both fermentations performed under those respective operating conditions, as demonstrated by nearly the same values of volumetric ($Q_p$) and specific ($q_p$) IA production rates, IA production yield ($Y_{p/s}$), and specific growth rate (${\mu}$). Specifically, the negligible difference of the specific growth rate (${\mu}$) between the two cultures (i.e., $0.029h^{-1}$ vs. $0.031h^{-1}$) was notable, considering the fact that ${\mu}$ normally has a significant influence on $q_p$ in the biosynthesis of secondary metabolites such as itaconic acid.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.343-346
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• 2001

The effect of agitation speed and aeration rate on mTG production and cell growth by Streptoverticillum morbarense was investigated. Dissolved oxygen was controlled by on-line computer-controlled fermentation system. The agitation speed and aeration rate of 2.5 L fermentor ranged from 330 to 360 게m and 1 vvm to 4 vvm, respectively. The highest mTG production was 2.1 U/mL when dissolved oxygen level was 20%, and it was improved almost 1.1 times in comparison with that without dissolved uxygen control.

• 한국미생물·생명공학회지
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• 제16권6호
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• pp.450-456
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• 1988

대장균 변이주를 이용한 L-트립토판의 최적생산을 위해 목적산물의 생산과 유기산의 생성과의 상호관계를 조사한 결과 비 산생성속도(specific acid production rate)가 증가할수록 L-트립토판의 생산이 감소하는 것으로 나타났다. 따라서 L-트립토판 발효시 산의 생성량을 줄이기 위해 조절식 유가배양법을 도입하였는데 이 배양공정에서는 배양액내의 용존산소농도에 따라 영양배지의 유가속도를 조절하는 방식을 사용하여 세포증식속도를 제한, 세포의 산소요구량이 공급량을 초과하지 않도록 하였다. 이러한 조절식 유가배양법으로 대장균 세포를 배양한 결과 기존의 유가배양식에 비해 비 산생성속도가 현저하게 감소하였으며 L-트립토판의 생산은 5배 정도나 증가되었다.

• KSBB Journal
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• 제14권6호
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• pp.672-676
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• 1999

캡슐고정화 Aspergillus niger를 이용하여 산소공급이 구연산의 생산에 미치는 영향을 조사하였다. 칼슘알지네이트 캡슐에 고정화된 A. niger는 배양중 성장하여 2일 후에는 균사가 캡슐막을 뚫고 나왔으며 배양 8일 후에는 균사가 캡슐전체를 뒤덮었다. 배양액중의 질소원이 충분하거나 산소가 부족한 경우 균사가 느슨해졌다. 일정한 성장용액의 양에 미생물고정화 캡슐의 양이 많이 투입될 수록 구연산의 생산량은 감소하였다. 플라스크 배양의 경우 부피산소전달계수($K_La$)가 1.8 $hr^{-1}$에서 2.55 $hr^{-1}$로 증가하면 미생물의 성장속도는 증가하지만 구연산의 생산량에는 큰 영향이 없었다. 축중심 공기 부양반응기 내에서의 산소전달 속도증가 ($K_La=150hr^{-1}$)는 미생물의 성장속도는 크게 촉진시켰지만 구연산의 생산량은 오히려 감소시켰다. 그러나 중심축 공기 부양반응기내에서 성장배지 중의 질소원 농도를 감소시키면 플라스크 배양의 생산량보다 약 40%이상 증산할 수 있었다. 뿐만 아니라 최대생산량을 얻는 최적 발효기간도 3일 정도 단축시킬 수 있었다. 캡슐고정화 미생물의 성장이나 구연산 생산량은 중심축 공기 부양반응기의 구조변화에 큰 영향을 받지 않았다.

• 멤브레인
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• 제4권1호
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• pp.1-8
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• 1994

There are growing needs to produce relatively high purity(99.0% or higher) oxygen at low cost. For small scale production, both pressure swing adsorption(PSA) and membrane process are competitive and less expensive or more convenient than well known cryogenic fractionation technology. A continuous membrane column(CMC) combined with a PSA oxygen generator can be employed to produce high purity oxygen continuously. The oxygen enriched gas generated by a PSA unit, with a concentration of 93~94%, is fed to the CMC that consism of three modules of poly(imide) hollow fibers. Several experiments were conducted by varying parameters, such as feed flow rate, transmembrane pressure drop, stage cut, and feed location in order to obtain a high oxygen concentration above 99.0%. A two-series unit mode was also employed with CMC operation to optimize the given membrane area.

• 한국막학회:학술대회논문집
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• 한국막학회 1994년도 심포지움시리즈 Jan-94 기체분리막 기술 및 응용
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• pp.1-21
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• 1994

There are growing needs to produce relatively high purity (99.0% or higher) oxygen at low cost. For small scale production, both pressure swing adsorption (PSA) and membrane process are competitve and less expensive or more convient than well known crygenic fractionation technology. A continuous membrane colume (CMC) combined with a PSA oxygen generator can be employed to produce high purity oxygen continuosly. The oxygen-enriched gas generated by a PSA unit, with a concentration of 93-94%, is fed to the CMC that consists of three modules of poly(imide) hollow fibers. Several experiments were conducted by varying parameters, such feed flow rate, transmenbrane pressure drop, stage cut, and feed location in order to obtain a high oxygen concentration above 99.0%. A two-series unit mode was also employed with CMC operation to optimize the given membrane area.