Dynamic flux balance analysis for pharmaceutical protein production by Pichia pastoris: Human growth hormone

Date

2011-03-07

Author

Çalık, Pınar
Taspinar, Hatice
Soyaslan, Elif S.
Inankur, Bahar

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The influence of methanol feeding rate on intracellular reaction network of recombinant human growth hormone (rhGH) producing Pichia pastoris was investigated at three different specific growth rates, namely, 0.02 (MS-0.02), 0.03 (MS-0.03), and 0.04h(-1) (MS-0.04) where Period-I (33 <= t < 42 h) includes the early exponential growth phase; Period-II (42 <= t < 48 h) is the exponential growth phase where the specific cell growth rate decreases; Period-III (48 <= t <= 51 h) is the exponential growth phase where rhGH concentration was the highest; and Period-IV (t > 51 h) is the diminution phase for rhGH and cell synthesis. In Period-I, almost all of the formaldehyde entered the assimilatory pathway, at MS-0.02 and MS-0.03, whereas, at MS-0.04 high methanol feeding rate resulted in an adaptation problem. In Period-III, only at MS-0.02 co-carbon source sorbitol uptake-flux was active showing that sorbitol uptake does not affected from the predetermined feeding rate of methanol at mu(0) > 0.02 h(-1). The biomass synthesis flux value was the highest in Period-I, -II and -III, respectively at MS-0.03 & MS-0.04, MS-0.04 and MS-0.02; whereas, rhGH flux was the highest in Period-I, -II, and -III, respectively at MS-0.03, MS-0.02 and MS-0.03. Based on the fluxes, Period-I should start with MS-0.03 methanol feeding rate and starting from the middle of Period-II methanol feeding rate should be shifted to MS-0.02. (c) 2010 Elsevier Inc. All rights reserved.

Subject Keywords

Biotechnology, Applied Microbiology and Biotechnology, Biochemistry

URI

https://hdl.handle.net/11511/34439

Journal

ENZYME AND MICROBIAL TECHNOLOGY

DOI

https://doi.org/10.1016/j.enzmictec.2010.09.016

Collections

Department of Chemical Engineering, Article

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Citation Formats

P. Çalık, H. Taspinar, E. S. Soyaslan, and B. Inankur, “Dynamic flux balance analysis for pharmaceutical protein production by Pichia pastoris: Human growth hormone,” ENZYME AND MICROBIAL TECHNOLOGY, pp. 209–216, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/34439.