Modeling the growth and proteinase A production in continuous cultures of recombinant Saccharomyces cerevisiae

Morten Carlsen, Kirsten Væver Jochumsen, Claus Emborg, Jens Bredal Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Overexpression of the homologous protein proteinase A (PrA) in Saccharomyces cerevisiae has been achieved by inserting the PrA gene (PEP4) with its own promoter on a 2 mu multicopy plasmid. With this system the specific PrA production rate was found to be described well by a linear function of the oxidative glucose metabolism, the reductive glucose metabolism, and the oxidative ethanol metabolism, with a significant lower yield resulting from the reductive glucose metabolism compared with the oxidative glucose metabolism. To describe the experimental data, a simple mathematical model has been set up. The model is based on an assumption of a limited respiratory capacity as suggested by Sonnleitner and Kappeli but extended to describe production of an extracellular protein. The model predicts correctly the critical dilution rate to be between 0.15 and 0.16 h(-1), the decrease in the biomass yield above the critical dilution rate, and the production of proteinase A at different dilution rates. Both the experimental data and model simulations suggest that the optimum operating conditions for protein production is just at the critical dilution rate. (C) 1997 John Wiley & Sons, Inc.
    Original languageEnglish
    JournalBiotechnology and Bioengineering (Print)
    Volume55
    Issue number2
    Pages (from-to)447-454
    ISSN0006-3592
    DOIs
    Publication statusPublished - 1997

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