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Systems metabolic engineering of microorganisms for natural and non-natural chemicals

Abstract

Growing concerns over limited fossil resources and associated environmental problems are motivating the development of sustainable processes for the production of chemicals, fuels and materials from renewable resources. Metabolic engineering is a key enabling technology for transforming microorganisms into efficient cell factories for these compounds. Systems metabolic engineering, which incorporates the concepts and techniques of systems biology, synthetic biology and evolutionary engineering at the systems level, offers a conceptual and technological framework to speed the creation of new metabolic enzymes and pathways or the modification of existing pathways for the optimal production of desired products. Here we discuss the general strategies of systems metabolic engineering and examples of its application and offer insights as to when and how each of the different strategies should be used. Finally, we highlight the limitations and challenges to be overcome for the systems metabolic engineering of microorganisms at more advanced levels.

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Figure 1: Categories of chemicals produced by microbial cell factories.
Figure 2: Construction of synthetic metabolic pathways in a noninherent host strain.
Figure 3: Strategies for substrate utilization engineering.
Figure 4: Byproduct elimination, precursor enrichment and transporter engineering.
Figure 5: Rerouting of metabolic pathways.
Figure 6: In silico- and omics-based target gene selection and strain development based on pathway prediction and in silico simulation.
Figure 7: Strategies for optimization and modulation of metabolic pathways and rational-random metabolic engineering.

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Acknowledgements

We thank H.U. Kim for helpful discussion. This work was supported by the Advanced Biomass Research and Development Center of Korea (ABC-2010-0029799) through the Global Frontier Research Program (GFRP) of the Ministry of Education, Science and Technology (MEST) and also by the Intelligent Synthetic Biology Center (2011-0031963) through the GFRP of MEST. We also thank the World Class University program (R32-2008-000-10142-0) of MEST for additional support.

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Lee, J., Na, D., Park, J. et al. Systems metabolic engineering of microorganisms for natural and non-natural chemicals. Nat Chem Biol 8, 536–546 (2012). https://doi.org/10.1038/nchembio.970

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