cfaed Seminar Series
cfAED Seminar Series
Dipl.-Ing. Alexander Grünberger , Forschungszentrum Jülich GmbH (Juelich Research Center), Germany
Single-cell Bioreactors boost Bioprocess Development: New Insights into Cellular Metabolism
08.10.2014 (Wednesday)
, 15:00 - 16:30
TU Dresden, Mierdel-Bau, Nöthnitzer Str. 64, room 116 , Georg-Schumann-Str. 11 , 01187 Dresden
Today, several national and international initiatives are concerned with the establishment of a sustainable biobased economy. Among other efforts, industrially applied microbial cell factories, converting renewable carbon sources into valuable products, will play a major role in this challenging development process. Therefore, the continuous improvement of biobased production processes and the complete understanding of the underlying microbial cell factories is essential. Microfluidic single-cell cultivation (MSCC) systems offer a unique method to investigate cell-to-cell heterogeneity at constant or defined oscillating environmental conditions imitating large-scale bioreactors [1-2].
Microscale Bioengineering Group, IBG-1: Biotechnology (Alexander Grünberger, Christopher Probst, Wolfgang Wiechert and Dietrich Kohlheyer)
Corynebacterium glutamicum, which is an industrial workhorse for amino acid production, was analyzed at single-cell level to gain novel insides into industrial bioprocesses. The growth rate of C. glutamicum wildtype under various environmental conditions was investigated systematically. Surprisingly, single-cell cultivations in a continuously perfused microfluidic bioreactor system revealed elevated growth rates (μ=0.62±0.02 h-1) in contrast to large-scale batch cultivations (μ=0.42±0.02 h-1) [3]. Based on these findings, potential effectors were investigated. It was found that protocatechuate - an iron chelator -, significantly influences growth rates of C. glutamicum [4].
Furthermore, the L-valine producer C. glutamicum ΔaceE was investigated by means of our recently developed genetically encoded fluorescence reporter systems for the intracellular detection of amino-acids at single-cell resolution [5]. Interestingly, the strain exhibited a strong population heterogeneity with respect to growth as well as productivity with individual cells expressing different fluorescence levels. Latest results will be discussed in the presentation.
Our results demonstrate that microfluidic picoliter bioreactors are powerful tools to gain single-cell knowledge of biotechnological processes essential for upcoming process optimization and research. Nevertheless, single-cell bioreactors are still in an early phase of development, making a critical discussion of advantages, disadvantages, existing challenges and necessary improvements necessary.
[1] Grünberger, A., et al., 2014, Current Opinion in Biotechnology, 29:15-23.
[2] Grünberger, A., et al., 2012, Lab on a Chip, 12(11): 2060-2068.
[3] Grünberger, A., et al., 2013, Biotechnology and Bioengineering, 110(1): 220-228.
[4] Unthan, S., et al., 2014, Biotechnology and Bioengineering, 111(2):359-371.
[5] Mustafi, N., et al., 2014, Plos one, 14(4): 9:e85731.