• Journal of Microbiology and Biotechnology
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• 제31권3호
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• pp.349-357
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• 2021

Monoclonal antibodies are widely used as diagnostic reagents and for therapeutic purposes, and their demand is increasing extensively. To produce these proteins in sufficient quantities for commercial use, it is necessary to raise the output by scaling up the production processes. This review describes recent trends in high-density cell culture systems established for monoclonal antibody production that are excellent methods to scale up from the lab-scale cell culture. Among the reactors, hollow fiber bioreactors contribute to a major part of high-density cell culture as they can provide a tremendous amount of surface area in a small volume for cell growth. As an alternative to hollow fiber reactors, a novel disposable bioreactor has been developed, which consists of a polymer-based supermacroporous material, cryogel, as a matrix for cell growth. Packed bed systems and disposable wave bioreactors have also been introduced for high cell density culture. These developments in high-density cell culture systems have led to the monoclonal antibody production in an economically favourable manner and made monoclonal antibodies one of the dominant therapeutic and diagnostic proteins in biopharmaceutical industry.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권4호
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• pp.288-305
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• 2000

A review on the main aspects associated with yeast flocculation and its application in biotechnological processes is presented. This subject is addressed following three main aspects-the basics of yeast flocculation, the development of "new" flocculating yeast strains and bioreactor development. In what concerns the basics of yeast flocculation, the state of the art on the most relevant aspects of mechanism, physiology and genetics of yeast flocculation is reported. The construction of flocculating yeast strains includes not only the recombinant constitutive flocculent brewer's yeast, but also recombinant flocculent yeast for lactose metabolisation and ethanol production. Furthermore, recent work on the heterologous $\beta$-galactosidase production using a recombinant flocculent Saccharomyces cerevisiae is considered. As bioreactors using flocculating yeast cells have particular properties, mainly associated with a high solid phase hold-up, a section dedicated to its operation is presented. Aspects such as bioreactor productivity and culture stability as well as bioreactor hydrodynamics and mass transfer properties of flocculating cell cultures are considered. Finally, the paper concludes describing some of the applications of high cell density flocculating bioreactors and discussing potential new uses of these systems.e systems.

• Journal of Microbiology and Biotechnology
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• 제31권10호
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• pp.1430-1437
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• 2021

Cronobacter sakazakii is an opportunistic pathogenic bacterium found in powdered infant formula and is fatal to neonates. Antibiotic resistance has emerged owing to overuse of antibiotics. Therefore, demand for high-yield bacteriophages as an alternative to antibiotics has increased. Accordingly, we developed a modified mass-production method for bacteriophages by introducing a two-stage self-cycling (TSSC) process, which yielded high-concentration bacteriophage solutions by replenishing the nutritional medium at the beginning of each process, without additional challenge. pH of the culture medium was monitored in real-time during C. sakazakii growth and bacteriophage CS01 propagation, and the changes in various parameters were assessed. The pH of the culture medium dropped to 5.8 when the host bacteria reached the early log phase (OD₅₄₀ = 0.3). After challenge, it decreased to 4.65 and then recovered to 4.94; therefore, we set the optimum pH to challenge the phage at 5.8 and that to harvest the phage at 4.94. We then compared phage production during the TSSC process in jar-type bioreactors and the batch culture process in shaker flasks. In the same volume of LB medium, the concentration of the phage titer solution obtained with the TSSC process was 24 times higher than that obtained with the batch culture process. Moreover, we stably obtained high concentrations of bacteriophage solutions for three cycles with the TSSC process. Overall, this modified TSSC process could simplify large-scale production of bacteriophage CS01 and reduce the unit cost of phage titer solution. These results could contribute to curing infants infected with antibiotic-resistant C. sakazakii.

• 한국미생물·생명공학회지
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• 제45권3호
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• pp.185-199
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• 2017

메탄은 자연적인 발생원과 인위적인 발생원에 의해 배출되며 지구온난화를 야기하는 대표적인 온실가스이다. 메탄을 탄소원과 에너지원으로 이용하는 메탄산화세균은 메탄의 생물학적 산화에 중요한 역할을 한다. 메탄산화세균의 서식지는 매우 다양하며 메탄산화반응의 핵심 효소인 methane monooxygenases (MMOs)는 메탄뿐 아니라 다른 기질을 산화할 수 있는 기질특이성을 가지고 있다. 이러한 메탄산화세균의 특성으로 인해 생물학적 메탄 저감 기술과 생물정화기술 분야에서 메탄산화세균의 활용에 대한 연구가 활발히 진행되고 있다. 본 총설 논문에서는 메탄산화세균의 종류, MMOs의 특성과 메탄산화세균의 고농도 배양 기술에 관한 최근 정보를 정리하였다. 또한 메탄산화세균을 이용한 생물학적 메탄 저감 관련 실험실 규모와 매립지 현장에서의 기술 개발 현황 및 적용 결과를 소개하였다. 이러한 생물학적 메탄 저감 시스템에서 메탄산화세균의 군집 거동 특성도 고찰하였다. 마지막으로, 메탄산화세균을 활용한 생물공학기술의 혁신을 위해 필요한 과제로 대사활성이 우수하거나 신규 대사능력을 가진 메탄산화세균의 지속적인 탐색 연구, 고농도 세포 대량배양기술 개발 및 미생물 컨소시움(메탄산화세균과 비메탄산화세균의 컨소시움) 디자인 및 관리 기술 등이 필요함을 제안하였다.

• 한국환경농학회지
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• 제42권3호
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• pp.253-258
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• 2023

In the environment, chromium often exists in a highly mobile and toxic form of Cr(VI). Therefore, the reduction of Cr(VI) to less toxic Cr(III) is considered an effective remediation strategy for Cr(VI)-contamination. In this study, the biological reduction of hexavalent chromium was examined at the concentrations of 0.01 mM, 0.1 mM, and 1 mM Cr(VI) by the dissimilatory metal-reducing bacterium, Shewanella sp. HN-41 in the presence of ferric-citrate. With the relatively condensed cell densities, the aqueous phase Cr(VI) was reduced at the proportions of 42%, 23%, and 31%, respectively for the 0.01 mM, 0.1 mM, and 1 mM Cr(VI) incubations, while Fe(III)-citrate was reduced at 95%, 88%, and 73%, respectively. Although the strain HN-41 was not considered to reduce Cr(VI) as the sole electron acceptor for anaerobic metabolism in the preliminary experiment, it has been presumed that outer-membrane c-type cytochromes such as MtrC and OmcA reduced Cr(VI) in the presence of ferric-citrate as the electron acceptor. Since this study indicated the potential of relatively high cell density for Cr(VI) reduction, it might propose a bioremediation strategy for Cr(VI) removal from contaminated waters using engineered systems such as bioreactors employing high cell growths.

• 멤브레인
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• 제34권1호
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• pp.38-49
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• 2024

본 연구에서는 분리막 생물반응기(membrane bioreactor, MBR)에서 발생되는 생물막오염 완화에 탁월한 효과를 가진 분리막을 개발할 목적으로, 친수성 산소 기능기가 많은 탄소나노구체(carbon nanosphere, CNS)를 합성한 뒤, 이를 첨가제로 활용하여 친수성과 다공성 기공 구조를 갖는 고성능 한외여과막을 제조하였다. CNS는 막 표면에 초승달 모양의 기공을 형성하였고, CNS 함량을 4.6 wt%까지 증가시킴에 따라 최대기공 크기보다 큰 결함을 야기하지 않으면서 평균 표면 기공 크기를 약 40% 증가시키는 것으로 나타났다. 또한, CNS 복합막의 다공성 기공 구조는 CNS의 등방성 형태와 상대적으로 낮은 입자 수밀도 덕분에 CNS 첨가에 따른 고분자 용액의 점도 급등이 방지됐기 때문이라고 판단된다. 그러나 너무 다공성이 커지게 되면 기계적 물성이 저하되므로, 기공구조와 기계적 성질을 포함한 종합적인 고려를 했을 때 CNS2.3이 가장 우수하다고 관측되었다. CNS2.3은 CNS0에 비해 수투과도가 2배 이상 높을 뿐만 아니라, MBR 공정에서 분리막 세정이 요구될 때까지의 운전 시간도 5배 이상 연장시킨 것으로 확인되었다.