Holistic bioengineering: rewiring central metabolism for enhanced bioproduction
- Aslan, Selçuk Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, Potsdam-Golm 14476, Germany
- Noor, Elad Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, Zürich 8093, Switzerland
- Bar-Even, Arren Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, Potsdam-Golm 14476, Germany
- 2017-11-16
Published in:
- Biochemical Journal. - Portland Press Ltd.. - 2017, vol. 474, no. 23, p. 3935-3950
English
What does it take to convert a living organism into a truly productive biofactory? Apart from optimizing biosynthesis pathways as standalone units, a successful bioengineering approach must bend the endogenous metabolic network of the host, and especially its central metabolism, to support the bioproduction process. In practice, this usually involves three complementary strategies which include tuning-down or abolishing competing metabolic pathways, increasing the availability of precursors of the desired biosynthesis pathway, and ensuring high availability of energetic resources such as ATP and NADPH. In this review, we explore these strategies, focusing on key metabolic pathways and processes, such as glycolysis, anaplerosis, the TCA (tricarboxylic acid) cycle, and NADPH production. We show that only a holistic approach for bioengineering — considering the metabolic network of the host organism as a whole, rather than focusing on the production pathway alone — can truly mold microorganisms into efficient biofactories.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1042/bcj20170377
- ISSN 0264-6021
- Persistent URL
- https://sonar.ch/global/documents/66552
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