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High Cell Density Fermentation of Recombinant Escherichia coli with Computer‐Controlled Optimal Growth Rate
Author(s) -
KNORRE W. A.,
DECKWER W.D.,
KORZ D.,
POHL H.D.,
RIESENBERG D.,
ROSS A.,
SANDERS E.,
SCHULZ V.
Publication year - 1991
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1991.tb18592.x
Subject(s) - fermentation , bioreactor , escherichia coli , recombinant dna , microorganism , cell growth , biology , biochemistry , chemistry , industrial fermentation , bioprocess , growth rate , food science , microbiology and biotechnology , bacteria , gene , genetics , botany , paleontology , geometry , mathematics
In recent years recombinant DNA technology has enabled us to produce various proteins of therapeutic importance with microorganisms. As an appropriate host organism, E. coli plays a dominant role. Yields of E. coli dry cell mass in shaker flask culture range from 1-2 g/L, whereas in fermentors up to 10 g dry cells/L can be achieved. ZIMET and GBF have developed a high cell density fermentation process that produces E. coli (on a glucose/mineral salt medium) up to more than 100 g dry cells/L in a special fed-batch mode. This cultivation strategy prevents oxygen limitation and hence the accumulation of acetate and other metabolic byproducts. The specific growth rate can be adjusted so that product formation reaches its optimum value. An example of the production of alpha1-interferon is presented. The high cell density fermentations were realized in 30- and 450-L Chemap fermentors (ZIMET) and in a three-stage bioreactor scale-up system (72, 300, and 1,500 L) developed in cooperation with GBF and B. Braun Melsungen AG. Multiloop controllers were used to control the process variables.