279099 Strain Engineering to Control a Product Quality Attribute in Escherichia Coli Recombinant Protein Production Process

Wednesday, October 31, 2012
Hall B (Convention Center )
Karthik Veeravalli, Late Stage Cell Culture, Genentech, Inc., South San Francisco, CA

Strain engineering to control a product quality attribute in Escherichia coli recombinant protein production processes

 Continuous or bolus feeding of nutrients is commonly used in E. coli recombinant protein production processes to control different product quality attributes (PQAs). Although these strategies are effective in controlling PQAs, there are several operational disadvantages associated with continuous or bolus feeding. Additions to the culture increase the operational complexity and the overall cost of the fermentation process. In addition, these nutrient feeds lead to undesirable dilution of the fermentation medium resulting in lower cell densities and possibly lower product yields. An attractive alternative to using these feeding strategies, where applicable, is to engineer hosts that can control particular PQAs.  In this work, we engineered the genome of an E. coli host expressing a recombinant protein product to control a PQA in the absence of the nutrient feeding. Furthermore, we show that the fermentation process performance utilizing the engineered host was comparable to the standard host for the recombinant protein production process.

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