A mathematical model is proposed to describe how the parametric dependences (sensitivities) of key process variables in a continuous flow fermenter using recombinant microorganisms vary with time. Solution of the model, with typical values for the parameters, indicates that most sensitivities incre
Non-invasive detection of the metabolic burden on recombinant microorganisms during fermentation processes
✍ Scribed by Th Bachinger; C -F Mandenius; G Striedner; F Clementschitsch; E Dürrschmid; M Cserjan-Puschmann; O Doblhoff-Dier; K Bayer
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2001
- Tongue
- English
- Weight
- 211 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0268-2575
- DOI
- 10.1002/jctb.463
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✦ Synopsis
Abstract
Heterologous protein production is an important source of therapeutic products. Optimisation of such bioprocesses by adjustment of the expression rate of the heterologous protein to the biosynthetic capacity of the cell metabolism would benefit from an online method for monitoring the metabolic burden. In this study we evaluated the use of a chemical multi‐sensor array for this purpose. Fermentations with a recombinant Escherichia coli strain expressing human superoxide dismutase (rhSOD) were monitored by the sensor array. The results of isopropyl‐thiogalactopyranoside (IPTG)‐induced expression were compared with fermentations with a plasmid‐free strain. The overproduction of rhSOD, imposing a high metabolic burden on the plasmid‐carrying cells, was distinctly and reproducibly observed by the multi‐sensor array. The potential of this non‐invasive method of non‐specific metabolic burden monitoring is demonstrated by the results of the study.
© 2001 Society of Chemical Industry
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