High Level Secretion of Recombinant Human Serum Albumin by Fed-Batch Fermentation of the Methylotrophic Yeast, Pichia pastoris, Based on Optimal Methanol Feeding Strategy

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概要

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• The dynamic programming method was applied to obtain the optimal specific growth rate, μ, in the fed-batch fermentation using the recombinant human serum albumin (rHSA)-producing yeast, Pichia pastoris. Based on the relationship between the specific production rate, ρ, and the specific growth rate, μ, a simple mathematical model describing the growth and rHSA production was constructed and used for calculations. Two constraints, final volume and maximum methanol feed rate, were adopted for calculations and the optimal μ resulted as follows. That is, μ was initially at the maximum value, μ_<max> then decreased gradually. Finally, μ decreased to the μ_<min> that gave a maximum ρ. The decline of μ was revealed to be caused by the constraint for maximum methanol feeding rate, F_<max> and F_<max> was constaint until μ decreased to μ_<min>. We tried to realize the optimal μ in the fed-batch fermentation by manipulating the methanol feeding rate and obtained it. However, the observed ρ was differed from the expected one. The discrepancy between the expected ρ and observed ρ after the change of μ suggests the inapplicability of the relationship between μ and ρ to dynamic situations where μ changes. To confirm this, simulation and fed-batch fermentation runs were carried out at a methanol feeding rate that would cause a continuous change in μ. The rHSA production was simulated well, suggesting the applicability of the relationship between μ and ρ in such situations. Discontinuity in the change in methanol feeding rate of the optimal feed pattern at the time μ changed is considered to be the cause for the discrepancy between the expected and observed ρ. Therefore, a new methanol feeding strategy that could mimic the changes in μ and ρ of the optimal strategy without a discontinuity in the feeding rate was sought using a mathematical model of fermentation by trial and error. This modification in the methanol feeding rate resulted in a considerably improved ρ and 18% increase in total rHSA production compared with those obtained by the optimal strategy.

• 社団法人日本生物工学会の論文
• 2000-09-25

著者

• Ohya Tomoshi

  Protein Research Laboratory Pharmaceutical Research Division Mitsubishi Pharma Corporation

• Ohya Tomoshi

  大阪大学 工学研究科生命先端工学専攻

• Ohya Tomoshi

  Protein Reserach Laboratories Pharmaceuticals Research Division Mitsubishi Pharma Corporation

• OHYAMA MASAO

  Protein Research Laboratory, Pharmaceutical Research Division, Mitsubishi Pharma Corporation

• KOBAYASHI KAORU

  Exploratory Research III, Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Cor

• KUWAE SHINOBU

  Exploratory Research III, Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Cor

• OHYA TOMOSHI

  Exploratory Research III, Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Cor

• OHDA TOYOO

  Exploratory Research III, Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Cor

• OHYAMA MASAO

  Exploratory Research III, Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Cor

• TOMOMITSU KENJI

  BIPHA Corporation

• Ohda Toyoo

  Bioscience Research Drug Discovery Laboratories Pharmaceutical Research Division Yoshitomi Pharmaceu

• Kobayashi Kaoru

  Protein Research Laboratory Pharmaceutical Research Division Mitsubishi Pharma Corporation

• Ohyama Masao

  Protein Research Laboratory Pharmaceutical Research Division Mitsubishi Pharma Corporation

• Kuwae Shinobu

  Protein Research Laboratory Pharmaceutical Research Division Mitsubishi Pharma Corporation

• Kuwae Shinobu

  Research Center For Cell And Tissue Culture Faculty Of Agriculture Kyoto University

• Kobayashi Kaoru

  Protein Research Laboratory Mitsubishi Tanabe Pharma Corporation

• Ohya Tomoshi

  Protein Research Laboratory Mitsubishi Tanabe Pharma Corporation

関連論文

• Overexpression of GADD34 Enhances Production of Recombinant Human Antithrombin III in Chinese Hamster Ovary Cells(CELL AND TISSUE ENGINEERING)
• Development of a Fed-Batch Culture Process for Enhanced Production of Recombinant Human Antithrombin by Chinese Hamster Ovary Cells(CELL AND TISSUE ENGINEERING)
• Production of Recombinant Human Antithrombin by Pichia pastoris(Microbial Physiology and Biotechnology)
• High-Level Production of Prourokinase-Annexin V Chimeras in the Methylotrophic Yeast Pichia pastoris (BIOCHEMICAL ENGINEERING)
• High Level Secretion of Recombinant Human Serum Albumin by Fed-Batch Fermentation of the Methylotrophic Yeast, Pichia pastoris, Based on Optimal Methanol Feeding Strategy
• Addition of Oleic Acid Increases Expression of Recombinant Human Serum Albumin by the AOX2 Promoter in Pichia pastoris
• High-Level Expression of Recombinant Human Serum Albumin from the Methylotrophic Yeast Pichia pastoris with Minimal Protease Production and Activation
• THE EFFECTS OF CODING REGION ON ITS GENE EXPRESSION IN THE Chlamydomonas CHLOROPLAST
• Effect of Coding Regions on Chloroplast Gene Expression in Chlamydomonas reinhardtii
• Derivation of a Glycerol-negative Mutant of a Methylotrophic Yeast, Candida boidinii, and Accumulation of Glycerol in Methanol Medium(Microbiology & Fermentation Industry)
• Overexpression of GADD34 Enhances Production of Recombinant Human Antithrombin III in Chinese Hamster Ovary Cells
• Production of Glycerol from Methanol by a Mutant Strain of Candida boidinii No. 2201

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