Improving fatty acids production by engineering dynamic pathway regulation and metabolic control
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- Peng Xu
- Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;
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- Lingyun Li
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180;
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- Fuming Zhang
- Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;
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- Gregory Stephanopoulos
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
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- Mattheos Koffas
- Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;
説明
<jats:title>Significance</jats:title> <jats:p>One important synthetic chemistry reaction endowed by nature is the decarboxylative carbon condensation reaction using malonyl-CoA as carbon donor. Previous metabolic engineering efforts centered on the malonyl-CoA–dependent pathway have resulted in the production of many value-added compounds. Here we mimicked the native biological systems and used a dynamic regulatory network to optimize production titers and yield. The naturally existing transcriptional regulator FapR was rewired to dynamically control gene expressions involved in the supply and consumption of malonyl-CoA. Applying this metabolic control allowed the engineered cell to dynamically regulate pathway expression and compensated the metabolic activity of critical enzymes. The synthetic malonyl-CoA switch engineered in this study opens up new venues for dynamic pathway optimization and efficient production of malonyl-CoA–derived compounds.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 111 (31), 11299-11304, 2014-07-21
Proceedings of the National Academy of Sciences