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Intensification of high cell-density cultivations of rE. coli for production of S. pneumoniae antigenic surface protein, PspA3, using model-based adaptive control

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Abstract

This work proposes an innovative methodology to control high density fed-batch cultures of E. coli, based on measurements of the concentration of dissolved oxygen and on estimations of the cellular specific growth rate (µ), of the yield of biomass/limiting substrate (Y xs) and of the maintenance coefficient (m). The underlying idea is to allow cells to grow according to their metabolic capacity, without the constraints inherent to pre-set growth rates. Cellular concentration was assessed on-line through a capacitance probe. Three configurations of the control system were compared: (1) pre-set value for the three control parameters; (2) continuously updating µ; (3) updating µ, Y xs and m. Implementation of an efficient noise filter for the signal of the capacitance probe was essential for a good performance of the control system. The third control strategy, within the framework of an adaptive model-based control, led to the best results, with biomass productivity reaching 9.2 gDCW/L/h.

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Acknowledgments

The authors would like to thank the São Paulo Research Foundation (FAPESP) and Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) for funding this work, and Tiago Martins Pereira and Amadeus Gomes de Azevedo for technical support.

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Authors and Affiliations

  1. Departamento de Engenharia Química, Universidade Federal de São Carlos, P.O. Box 676, São Carlos, SP, 13565-905, Brazil

    Antonio Carlos Luperni Horta, Cíntia Regina Sargo, Adilson José da Silva, Marina de Carvalho Gonzaga, Maurício Possedente dos Santos, Teresa Cristina Zangirolami & Roberto de Campos Giordano

  2. Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil

    Viviane Maimoni Gonçalves

Authors
  1. Antonio Carlos Luperni Horta
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  2. Cíntia Regina Sargo
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  3. Adilson José da Silva
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  4. Marina de Carvalho Gonzaga
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  5. Maurício Possedente dos Santos
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  6. Viviane Maimoni Gonçalves
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  7. Teresa Cristina Zangirolami
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  8. Roberto de Campos Giordano
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Correspondence to Roberto de Campos Giordano.

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Horta, A.C.L., Sargo, C.R., da Silva, A.J. et al. Intensification of high cell-density cultivations of rE. coli for production of S. pneumoniae antigenic surface protein, PspA3, using model-based adaptive control. Bioprocess Biosyst Eng 35, 1269–1280 (2012). https://doi.org/10.1007/s00449-012-0714-4

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  • DOI: https://doi.org/10.1007/s00449-012-0714-4

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