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Bioengineering 2014, 1(1), 47-61;

Quantifying the Effects of Frequency and Amplitude of Periodic Oxygen-Related Stress on Recombinant Protein Production in Pichia pastoris

Research Division Biochemical Engineering, Institute of Chemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1a, A-1060 Vienna, Austria
Author to whom correspondence should be addressed.
Received: 24 October 2013 / Revised: 25 November 2013 / Accepted: 2 December 2013 / Published: 18 December 2013
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Pichia pastoris is an attractive candidate platform for recombinant protein production. Dissolved oxygen is one of the most important factors in the cultivation of P. pastoris. However, the effect of oxygen on triggering productivity led to ambivalent results. In our earlier work, a two-compartment system, consisting of a single reactor coupled with a plug flow reactor (PFR), has been proposed as a tool to improve protein quantity and quality. The goal of this work was to investigate the effects of frequency (the residence time of broth in the PFR) and amplitude (the dissolved oxygen level in the reactor) of the stress on productivity, titer and physiology. A recombinant P. pastoris strain, which expressed horseradish peroxidase, was used as the model system. Thirteen experiments were performed. Multivariate data analysis was done and the results showed that the residence time did not influence titer, productivity and physiology over the range of residence time studied while dissolved oxygen influenced titer and specific productivity in a quadratic function. In other words, an intermediate level of dissolved oxygen (25%) showed the highest specific productivity and titter, irrespective of the residence time in the PFR. In turn, the variation of the residence time and dissolved oxygen did not influence growth physiology, as quantified in biomass and carbon dioxide yields. View Full-Text
Keywords: oxygen-related stress; two-compartment system; Pichia pastoris oxygen-related stress; two-compartment system; Pichia pastoris

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Jazini, M.; Cekici, G.; Herwig, C. Quantifying the Effects of Frequency and Amplitude of Periodic Oxygen-Related Stress on Recombinant Protein Production in Pichia pastoris. Bioengineering 2014, 1, 47-61.

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