Tracking the acetate threshold using DO-transient control during medium and high cell density cultivation of recombinantEscherichia coli in complex media

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
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 > Institute of Infection Immunity and Inflammation
Journal Name:Biotechnology and Bioengineering
Publisher:Wiley
ISSN:0006-3592
ISSN (Online):1097-0290
Published Online:21 August 2003

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