TY - JOUR
T1 - CO2/HCO3 − perturbations of simulated large scale gradients in a scale-down device cause fast transcriptional responses in Corynebacterium glutamicum
AU - Buchholz, Jens
AU - Graf, Michaela
AU - Freund, Andreas
AU - Busche, Tobias
AU - Kalinowski, Jörn
AU - Blombach, Bastian
AU - Takors, Ralf
N1 - Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - Cascade reactor
KW - Corynebacterium glutamicum
KW - Dissolved carbon dioxide
KW - Gradients
KW - Process inhomogeneity
KW - Scale-down
UR - http://www.scopus.com/inward/record.url?scp=84920252738&partnerID=8YFLogxK
U2 - 10.1007/s00253-014-6014-y
DO - 10.1007/s00253-014-6014-y
M3 - Article
C2 - 25139448
AN - SCOPUS:84920252738
SN - 0175-7598
VL - 98
SP - 8563
EP - 8572
JO - Applied Microbiology and Biotechnology
JF - Applied Microbiology and Biotechnology
IS - 20
ER -