A simple model-based control for Pichia pastoris allows a more efficient heterologous protein production bioprocess

Oriol Cos, Ramon Ramon, José Luis Montesinos, Francisco Valero

    Research output: Contribution to journalArticleResearchpeer-review

    31 Citations (Scopus)

    Abstract

    A predictive control algorithm coupled with a Pl feedback controller has been satisfactorily implemented in the heterologous Rhizopus oryzae lipase production by Pichia pastoris methanol utilization slow (Mutss) phenotype. This control algorithm has allowed the study of the effect of methanol concentration, ranging from 0.5 to 1.75 g/L, on heterologous protein production. The maximal lipolytic activity (490 UA/mL), specific yield (11,236 UA/gbiomass), productivity (4,901 UA/L·h), and specific productivity (112 UA/gbiomassh were reached for a methanol concentration of 1 g/L. These parameters are almost double than those obtained with a manual control at a similar methanol set-point. The study of the specific growth, consumption, and production rates showed different patterns for these rates depending on the methanol concentration set-point. Results obtained have shown the need of implementing a robust control scheme when reproducible quality and productivity are sought. It has been demonstrated that the model-based control proposed here is a very efficient, robust, and easy-to-implement strategy from an industrial application point of view. © 2006 Wiley Periodicals, Inc.
    Original languageEnglish
    Pages (from-to)145-154
    JournalBiotechnology and Bioengineering
    Volume95
    DOIs
    Publication statusPublished - 5 Sep 2006

    Keywords

    • Fed-batch
    • Heterologous lipase production
    • Methanol monitoring
    • Model-based control
    • Pichia pastoris

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