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Bioreactor engineering using disposable technology for enhanced production of hCTLA4Ig in transgenic rice cell cultures
Author(s) -
Kwon JunYoung,
Yang YongSuk,
Cheon SuHwan,
Nam HyungJin,
Jin GiHong,
Kim DongIl
Publication year - 2013
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.24916
Subject(s) - bioreactor , aeration , industrial and production engineering , continuous stirred tank reactor , microbiology and biotechnology , biology , genetically modified rice , food science , chemistry , chromatography , pulp and paper industry , transgene , biochemistry , genetically modified crops , botany , ecology , gene , electrical engineering , engineering
Two kinds of disposable bioreactors, air‐lift disposable bioreactors (ADB) and wave disposable bioreactors (WDB) were compared with stirred‐tank reactors (5‐L STR). These bioreactors were successfully applied to transgenic rice cell cultures for the production of recombinant human cytotoxic T‐lymphocyte antigen 4‐immunoglobulin (hCTLA4Ig). In both systems, a fed‐batch culture method was used to produce hCTLA4Ig efficiently by feeding concentrated amino acids and production levels were enhanced when dissolved oxygen (DO) level was regulated at 30% using pure oxygen sparging. Agitation and aeration rate during cultivation in ADB and WDB were determined by the same mixing time. The results in both disposable bioreactors showed similar values in maximum cell density (11.9 gDCW/L and 12.6 gDCW/L), doubling time (4.8‐ and 5.0‐day), and maximum hCTLA4Ig concentration (43.7 and 43.3 mg/L). Relatively higher cell viability was sustained in the ADB whereas hCTLA4Ig productivity was 1.2‐fold higher than that in WDB. The productivity was improved by increasing aeration rate (0.2 vvm). Overall, our experiments demonstrate pneumatically driven disposable bioreactors are applicable for the production of recombinant proteins in plant cell cultures. These results will be useful for development and scale‐up studies of disposable bioreactor systems for transgenic plant cell cultures. Biotechnol. Bioeng. 2013; 110:2412–2424. © 2013 Wiley Periodicals, Inc.