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  • Review Article
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Exploiting biological complexity for strain improvement through systems biology

Abstract

Cellular complexity makes it difficult to build a complete understanding of cellular function but also offers innumerable possibilities for modifying the cellular machinery to achieve a specific purpose. The exploitation of cellular complexity for strain improvement has been a challenging goal for applied biological research because it requires the coordinated understanding of multiple cellular processes. It is therefore pursued most efficiently in the framework of systems biology. Progress in strain improvement will depend not only on advances in technologies for high-throughput measurements but, more importantly, on the development of theoretical methods that increase the information content of these measurements and, as such, facilitate the elucidation of mechanisms and the identification of genetic targets for modification.

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Figure 1: Accumulated system-insight drives the systems biology cycle for strain improvement.
Figure 2: Identification of gene targets using global, stoichiometric modeling (H.A., Yong-Su Jin, J.M., G.S., unpublished data).
Figure 3: Exploiting complexities in metabolic networks.
Figure 4: Approaches for pattern modeling useful in association analysis.
Figure 5: Use of metabolic state assays for phenotypic characterization.
Figure 6: Determining active pathways after removing a transcription factor repressor.

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Acknowledgements

We acknowledge the DuPont-MIT Alliance for research support and Kyle Jensen for his helpful suggestions.

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Correspondence to Gregory Stephanopoulos.

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The authors declare no competing financial interests.

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Stephanopoulos, G., Alper, H. & Moxley, J. Exploiting biological complexity for strain improvement through systems biology. Nat Biotechnol 22, 1261–1267 (2004). https://doi.org/10.1038/nbt1016

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