Johnston, W. A., Stewart, M., Lee, P. and Cooney, M. J. (2003) Tracking the acetate threshold using DO-transient control during medium and high cell density cultivation of recombinantEscherichia coli in complex media. Biotechnology and Bioengineering, 84(3), pp. 314-323. (doi: 10.1002/bit.10772)
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Publisher's URL: http://dx.doi.org/10.1002/bit.10772
Abstract
DO-transient nutrient controllers use the dissolved oxygen signal to attempt acetate threshold tracking during fed-batch cultivation of recombinant E. coli. Here we apply DO-transient control to the production of Jembrana disease virus protein in complex Super Luria medium and compare performance against a high-limit pH-stat controller. For induction at medium cell density (harvest between 31 and 32.5 g dcw L) a total productivity of 0.27 g L h was achieved as compared to 0.24 g L h with the high-limit pH-stat. For induction at high cell density (harvest at 60 g dcw L), decreased productivity (0.12 g L h) was attributed to the effect of acetate accumulation on recombinant protein formation and a concomitant lowering of the critical growth rate. Our results suggest that complex media provides a difficult environment for the application of acetate threshold tracking DO-transient control because of difficulties in re-oxidizing acetate, and apparent localized production of acetate below the production threshold (as detected by the DO-transient controller as SPOURcrit). Configuring the DO-transient controller to avoid aggressive threshold probing is suggested as a means to improve performance and reduce acetate accumulation in complex media.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Stewart, Dr Meredith |
Authors: | Johnston, W. A., Stewart, M., Lee, P., and Cooney, M. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Biotechnology and Bioengineering |
Publisher: | Wiley |
ISSN: | 0006-3592 |
ISSN (Online): | 1097-0290 |
Published Online: | 21 August 2003 |
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