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Fermentation is a foundational biotechnological process used to produce pharmaceuticals, biofuels, enzymes, and food additives. Among industrial strategies, batch and continuous fermentation are the two most widely applied. Although both rely on microbial conversion of substrates into desired products, they differ markedly in operation, productivity, and suitability for specific applications.Batch fermentation occurs in a closed system in which nutrient media and inoculum are added at the...
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Large-Scale Cell Production Based on GMP-Grade Dissolvable Porous Microcarriers
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Multi-stage high cell continuous fermentation for high productivity and titer.

Ho Nam Chang1, Nag-Jong Kim, Jongwon Kang

  • 1Department of Chemical and Biomolecular Engineering, KAIST (Korea Advanced Institute of Science and Technology), Daejeon, Korea. hnchang@kaist.edu

Bioprocess and Biosystems Engineering
|December 4, 2010
PubMed
Summary

Multi-stage continuous high cell density culture (MSC-HCDC) significantly boosts fermentation productivity for lactic acid, penicillin, and ethanol. This advanced system offers higher titers and productivity compared to traditional batch or fed-batch methods.

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Area of Science:

  • Biotechnology
  • Biochemical Engineering
  • Industrial Microbiology

Background:

  • Traditional batch and fed-batch fermentation methods often face limitations in achieving high product titers and productivity.
  • Optimizing cell density and controlling fermentation kinetics are crucial for efficient bioprocesses.
  • Metabolite repression, such as glucose repression in penicillin production, necessitates advanced feeding strategies.

Purpose of the Study:

  • To simulate and evaluate the performance of multi-stage continuous high cell density culture (MSC-HCDC) for industrial fermentation.
  • To compare the productivity and titer of MSC-HCDC with conventional batch and fed-batch systems.
  • To explore the potential of MSC-HCDC as a novel production platform for various fermentation products.

Main Methods:

  • Simulation of an n-serially connected continuous stirred-tank reactor (CSTR) system for MSC-HCDC.
  • Incorporation of hollow fiber cell recycling or cell immobilization for achieving high cell densities.
  • Modeling based on published fermentation kinetics for lactic acid, penicillin, and ethanol production.

Main Results:

  • An 8-stage MSC-HCDC for lactic acid achieved 212.9 g/L titer and 10.6 g/L/h productivity, significantly outperforming fed-batch.
  • Penicillin production models predicted increased productivity with MSC-HCDC, reaching 149% and 289% in different configurations.
  • A 2-stage MSC-HCDC for ethanol showed 107% titer and 257% productivity compared to batch fermentation.

Conclusions:

  • MSC-HCDC offers substantially higher productivity than batch/fed-batch systems while maintaining or improving product titer.
  • The system's productivity advantage is linked to its dilution rate and the cycle time of batch/fed-batch processes.
  • MSC-HCDC is proposed as a versatile and efficient platform for producing diverse fermentation products, including monoclonal antibodies.