Maximizing recombinant human serum albumin production in a Muts Pichia pastoris strain |
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| Authors: | Muralidhar Mallem Shannon Warburton Fang Li Ishaan Shandil Adam Nylen Sehoon Kim Youwei Jiang Michael Meehl Marc d'Anjou Terrance A. Stadheim Byung‐Kwon Choi |
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| Affiliation: | GlycoFi, Biologics Discovery, Lebanon, NH |
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| Abstract: | Human serum albumin (HSA) is a cysteine rich molecule that is most abundant in human blood plasma. To remain viable in the market due to lower marketing costs for HSA, it is important to produce a large quantity in an economical manner by recombinant technology. The objective of this study was to maximize recombinant HSA (rHSA) production using a Muts Pichia pastoris strain by fermentation process optimization. We evaluated the impact of process parameters on the production of rHSA, including induction cell density (wet cell weight, g/L) and the control of specific growth rate at induction. In this study, we demonstrated that induction cell density is a critical factor for high level production of rHSA under controlled specific growth rate. We observed higher specific productivities at higher induction cell densities (285 g/L) and at lower specific growth rates (0.0022–0.0024/h) during methanol induction phase, and achieved the broth titer of rHSA up to 10 g/L. The temperature shift from 24 to 28oC was effective to control the specific growth rate at low level (≤0.0024/h) during methanol induction phase while maintaining high specific productivity [0.0908 mgrHSA/(gwcw h)]. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1488–1496, 2014 |
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| Keywords: | human serum albumin Pichia pastoris muts specific growth rate cell density |
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