Hypoxic fed-batch cultivation of Pichia pastoris increases specific and volumetric productivity of recombinant proteins

Kristin Baumann, Michael Maurer, Martin Dragosits, Oriol Cos, Pau Ferrer, Diethard Mattanovich

    Research output: Contribution to journalArticleResearchpeer-review

    94 Citations (Scopus)

    Abstract

    High cell density cultivation of Pichia pastoris has to cope with several technical limitations, most importantly the transfer of oxygen. By applying hypoxic conditions to chemostat cultivations of P. pastoris expressing an antibody Fab fragment under the GAP promoter, a 2.5-fold increase of the specific productivity qP at low oxygen supply was observed. At the same time the biomass decreased and ethanol was produced, indicating a shift from oxidative to oxidofermentative conditions. Based on these results we designed a feedback control for enhanced productivity in fed batch processes, where the concentration of ethanol in the culture was kept constant at approximately 1.0% (w_1) by a regulated addition of feed medium. This strategy was tested successfully with three different protein producing strains, leading to a three- to sixfold increase of the qP and threefold reduced fed batch times. Taken together the volumetric productivity Qp increased 2.3-fold. © 2007 Wiley Periodicals, Inc.
    Original languageEnglish
    Pages (from-to)177-183
    JournalBiotechnology and Bioengineering
    Volume100
    DOIs
    Publication statusPublished - 1 May 2008

    Keywords

    • Antibody fragment
    • Oxygen limitation
    • Pichia pastoris
    • Productivity
    • Trypsinogen

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