The purpose of this project is to derive strategies for increasing the productivity of
recombinant protein production processes by applying a systems biology perspective to
the phenomena occurring in the recombinant cell. This will specifically involve the use
of genome-scale analysis of the transcriptome, proteome and fluxome. Escherichia coli
have been the organism of choice for the production of many recombinant proteins with
high therapeutic value. However, there are still some associated phenomena that
decrease the process performance, like the stringent response that usually occurs when
very high levels of heterologous protein production. In this work, the high-cell density
fed-batch recombinant protein production process in E. coli will be studied, giving
particular relevance to stringent response. The approach is intended to be systematic, by
first compiling the existing knowledge about this phenomenon, extending existing
genome-scale models to accommodate that knowledge, and derive hypothesis in silico
that will then be tested by using genome-scale analysis of the transcriptome
