Multi-stage high cell continuous fermentation for high productivity and titer

Ho Nam Chang, Nag Jong Kim, Jongwon Kang, Chang Moon Jeong, Jin Dal Rae Choi, Qiang Fei, Byoung Jin Kim, Sunhoon Kwon, Sang Yup Lee, Jungbae Kim

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We carried out the first simulation on multi-stage continuous high cell density culture (MSC-HCDC) to show that the MSC-HCDC can achieve batch/fed-batch product titer with much higher productivity to the fed-batch productivity using published fermentation kinetics of lactic acid, penicillin and ethanol. The system under consideration consists of n-serially connected continuous stirred-tank reactors (CSTRs) with either hollow fiber cell recycling or cell immobilization for high cell-density culture. In each CSTR substrate supply and product removal are possible. Penicillin production is severely limited by glucose metabolite repression that requires multi-CSTR glucose feeding. An 8-stage C-HCDC lactic acid fermentation resulted in 212.9 g/L of titer and 10.6 g/L/h of productivity, corresponding to 101 and 429% of the comparable lactic acid fed-batch, respectively. The penicillin production model predicted 149% (0.085 g/L/h) of productivity in 8-stage C-HCDC with 40 g/L of cell density and 289% of productivity (0.165 g/L/h) in 7-stage C-HCDC with 60 g/L of cell density compared with referring batch cultivations. A 2-stage C-HCDC ethanol experimental run showed 107% titer and 257% productivity of the batch system having 88.8 g/L of titer and 3.7 g/L/h of productivity. MSC-HCDC can give much higher productivity than batch/fed-batch system, and yield a several percentage higher titer as well. The productivity ratio of MSC-HCDC over batch/fed-batch system is given as a multiplication of system dilution rate of MSC-HCDC and cycle time of batch/fed-batch system. We suggest MSC-HCDC as a new production platform for various fermentation products including monoclonal antibody.

Original languageEnglish
Pages (from-to)419-431
Number of pages13
JournalBioprocess and Biosystems Engineering
Volume34
Issue number4
DOIs
Publication statusPublished - 2011 May 1

    Fingerprint

Keywords

  • Antibody
  • Ethanol
  • High cell density
  • Lactic acid
  • Multi-stage continuous fermentation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering

Cite this

Chang, H. N., Kim, N. J., Kang, J., Jeong, C. M., Choi, J. D. R., Fei, Q., Kim, B. J., Kwon, S., Lee, S. Y., & Kim, J. (2011). Multi-stage high cell continuous fermentation for high productivity and titer. Bioprocess and Biosystems Engineering, 34(4), 419-431. https://doi.org/10.1007/s00449-010-0485-8