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Effect of preinduction specific growth rate on secretion of granulocyte macrophage colony stimulating factor by
C E Curless1, J Pope, L Loredo
1Amgen, Inc., Amgen Center, Thousand Oaks, California 93021.
Abstract:
The effect of preinduction specific growth rate on the rate of synthesis and processing of granulocyte macrophage colony stimulating factor (GMCSF) secreted by Escherichia coli was investigated. A chemostat was used to explore preinduction growth rates ranging from 0.038 to 0.2/h. The maximum yields of both total GMCSF and processed GMCSF were found to occur at a preinduction growth rate of 0.13/h. It was also discovered that if the postinduction feed rate is reduced at a preinduction growth rate near 0.13/h, then the same amount of processed GMCSF is formed, but no unprocessed GMCSF is produced. It was hypothesized that the rate of synthesis of total GMCSF increases with an increased preinduction specific growth rate, but translocation across the cytoplasmic membrane and processing is rate-limiting. Increased degradation of GMCSF during induction at higher preinduction specific growth rates decreased the amount of GMCSF produced.