Reverse Engineering of the Stress Response during Expression of a Recombinant Protein
نویسندگان
چکیده
The overexpression of recombinant proteins in microorganisms may lead to a metabolic depression or collapse of the cell factory. In order to understand this process and to optimize the cellular productivity the stress response was investigated. The expression of the recombinant human superoxide dismutase (SOD) was induced under steady state conditions and the expression of all 4289 protein coding genes of the microorganism Escherichia coli was monitored using microarrays. After normalization by the LOWESS method 102 differentially expressed genes were selected by a novel criterion that includes the measurement error. These differentially expressed genes were clustered using the EcoCyc database and the fuzzy-c-means clustering method. The results from clustering were interpreted in terms of dynamic models, which have been constructed either via Singular Value Decomposition (SVD) or a novel heuristic algorithm for dynamic model structure optimization.
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