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 Takors

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)8563-8572
Number of pages10
JournalApplied Microbiology and Biotechnology
Volume98
Issue number20
DOIs
StatePublished - Oct 2014
Externally publishedYes

Keywords

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

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