Applied Microbiology and Biotechnology

, Volume 98, Issue 20, pp 8563–8572 | Cite as

CO2/HCO3 perturbations of simulated large scale gradients in a scale-down device cause fast transcriptional responses in Corynebacterium glutamicum

  • Jens Buchholz
  • Michaela Graf
  • Andreas Freund
  • Tobias Busche
  • Jörn Kalinowski
  • Bastian Blombach
  • Ralf TakorsEmail author
Biotechnological products and process engineering


The exploration of scale-down models to imitate the influence of large scale bioreactor inhomogeneities on cellular metabolism is a topic with increasing relevance. While gradients of substrates, pH, or dissolved oxygen are often investigated, oscillating CO2/HCO3 levels, a typical scenario in large industrial bioreactors, is rarely addressed. Hereby, we investigate the metabolic and transcriptional response in Corynebacterium glutamicum wild type as well as the impact on l-lysine production in a model strain exposed to pCO2 gradients of (75–315) mbar. A three-compartment cascade bioreactor system was developed and characterized that offers high flexibility for installing gradients and residence times to mimic industrial-relevant conditions and provides the potential of accurate carbon balancing. The phenomenological analysis of cascade fermentations imposed to the pCO2 gradients at industry-relevant residence times of about 3.6 min did not significantly impair the process performance, with growth and product formation being similar to control conditions. However, transcriptional analysis disclosed up to 66 differentially expressed genes already after 3.6 min under stimulus exposure, with the overall change in gene expression directly correlateable to the pCO2 gradient intensity and the residence time of the cells.


Scale-down Process inhomogeneity Cascade reactor Dissolved carbon dioxide Gradients Corynebacterium glutamicum 



We thank Mira Lenfers-Lücker for the assistance with the HPLC analyses, as well as Maria Rahnert, Jennifer Pfizenmaier, and Salaheddine Laghrami for the support with the cascade bioreactor fermentations. The authors further gratefully acknowledge the funding of this work by the Deutsche Forschungsgemeinschaft (DFG), grant TA 241/5-1.

The authors

Supplementary material

253_2014_6014_MOESM1_ESM.pdf (366 kb)
ESM 1 (PDF 366 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jens Buchholz
    • 1
  • Michaela Graf
    • 1
  • Andreas Freund
    • 1
  • Tobias Busche
    • 2
  • Jörn Kalinowski
    • 2
  • Bastian Blombach
    • 1
  • Ralf Takors
    • 1
    Email author
  1. 1.Institute of Biochemical EngineeringUniversity of StuttgartStuttgartGermany
  2. 2.Microbial Genomics and BiotechnologyCenter for Biotechnology (CeBiTec)BielefeldGermany

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