Journal
JOURNAL OF BIOTECHNOLOGY
Volume 164, Issue 3, Pages 396-408Publisher
ELSEVIER
DOI: 10.1016/j.jbiotec.2012.08.026
Keywords
Recombinant proteins; Metabolism; High-throughput methods; Modelling; Systems biology
Categories
Funding
- MIT-Portugal Program in Bioengineering [MIT-Pt/BS-BB/0082/2008]
- research project HeliSysBio-Molecular Systems Biology Helicobacter pylori [FCT PTDC/EBB-EBI/104235/2008]
- Portuguese FCT (Fundacao para a Ciencia e Tecnologia) [SFRH/BD/22863/2005]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/22863/2005, MIT-Pt/BS-BB/0082/2008, PTDC/EBB-EBI/104235/2008] Funding Source: FCT
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Escherichia coli has been widely used for the production of recombinant proteins. However, the unbalances between host metabolism and recombinant biosynthesis continue to hamper the efficiency of these recombinant bioprocesses. The additional drainage of biosynthetic precursors toward recombinant processes burdens severely the metabolism of cells that, ultimately, elicits a series of stress responses, reducing biomass growth and recombinant protein production. Several strategies to overcome these metabolic limitations have been implemented; however, in most cases, improvements in recombinant protein expression were achieved at the expense of biomass growth arrest, which significantly hampers the efficiency of recombinant bioprocesses. With the advent of high throughput techniques and modelling approaches that provide a system-level understanding of the cellular systems, it is now expected that new advances in recombinant bioprocesses are achieved. By providing means to deal with these systems, our understanding on the metabolic behaviour of recombinant cells will advance and can be further explored to the design of suitable hosts and more efficient and cost-effective bioprocesses. Here, we review the major metabolic responses associated with recombinant processes and the engineering strategies relevant to overcome these stresses. Moreover, the advantages of applying systems levels engineering strategies to enhance recombinant protein production in E. coli cells are discussed and future perspectives on the advances of mathematical modelling approaches to study these systems are exposed. (c) 2012 Elsevier B.V. All rights reserved.
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