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Effects of dissolved oxygen tension and agitation rate on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors

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Abstract

Heat-shock protein glycoprotein (gp96) serves as a natural adjuvant for chaperoning antigenic peptide into the immune surveillance pathway. In our laboratory, MethA tumor cell suspension culture process has been recently developed for gp96 production in spinner flask. In this work, effects of dissolved oxygen tension (DOT) and agitation rate on this process were studied in stirred-tank bioreactor. The optimal conditions for gp96 production were different with those for MethA tumor cell growth. MethA tumor cell growth pattern was not much changed by various levels of DOT and agitation rate, while gp96 biosynthesis was more sensitive to DOT and agitation rate. Compared with 50% of DOT, the production and specific productivity of gp96 was increased by 27 and 66% at 10% of DOT, respectively. Compared with the agitation rate of 100 rpm, the production and volumetric productivity of gp96 was increased by 48 and 144% at the agitation rate of 200 rpm, respectively. Low DOT (i.e., 10% of air saturation) and high agitation rate (i.e., 200 rpm) were identified to be favorable for gp96 biosynthesis. The results of this work might be useful to scale-up the bioprocess into the pilot scale.

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Acknowledgment

The financial supports from the National Natural Science Foundation of China (NSFC, Project No. 20706012), National High Technology Research and Development Key Program of China (Project No. 2007AA021506), the Scientific Research Foundation for the Returned Overseas Chinese Scholars (Ministry of Personnel and State Education Ministry), Hubei Provincial Innovative Research Team in University (Project No. T200608), Hubei Provincial Science Foundation for Distinguished Young Scholars (Project No. 2006ABB034), Hubei Provincial International Cooperation Foundation for Scientific Research (Project No.2007CA012), the Science and Technology Commission of Wuhan Municipality “Chenguang Jihua” (Project No. 20065004116-31), the Scientific Research Key Foundation from Hubei University of Technology (Project No. 306.18002), and the Open Project Program of the State Key Laboratory of Bioreactor Engineering (ECUST) are gratefully acknowledged. The authors thank Nova Biomedical Corp. (MA, USA) for the loan of the BioProfile 200 Analysator, and Innovatis GmbH (Germany) for the loan of the Cedex® system. Ya-Jie Tang also thanks the Chutian Scholar Program from Hubei Provincial Department of Education, China (2006).

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Authors and Affiliations

  1. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

    Ya-Jie Tang, Hong-Mei Li & Jean-François P. Hamel

  2. Hubei Provincial Key Laboratory of Industrial Microbiology, College of Bioengineering, Hubei University of Technology, 430068, Wuhan, China

    Ya-Jie Tang & Hong-Mei Li

  3. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100080, Beijing, China

    Ya-Jie Tang

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  1. Ya-Jie Tang
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Correspondence to Ya-Jie Tang.

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Tang, YJ., Li, HM. & Hamel, JF.P. Effects of dissolved oxygen tension and agitation rate on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors. Bioprocess Biosyst Eng 32, 475–484 (2009). https://doi.org/10.1007/s00449-008-0267-8

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