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Curr Opin Chem Biol. 2017 Apr;37:56-62. doi: 10.1016/j.cbpa.2016.12.023. Epub 2017 Jan 30.

Synthetic metabolism: metabolic engineering meets enzyme design.

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Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology & LOEWE Research Center for Synthetic Microbiology (SYNMIKRO), Karl-von-Frisch-Str. 10, D-35043 Marburg, Germany. Electronic address:
Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, UK. Electronic address:
Systems and Synthetic Metabolism Group, Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Am Mühlenberg 1, D-14476 Potsdam, Germany.


Metabolic engineering aims at modifying the endogenous metabolic network of an organism to harness it for a useful biotechnological task, for example, production of a value-added compound. Several levels of metabolic engineering can be defined and are the topic of this review. Basic 'copy, paste and fine-tuning' approaches are limited to the structure of naturally existing pathways. 'Mix and match' approaches freely recombine the repertoire of existing enzymes to create synthetic metabolic networks that are able to outcompete naturally evolved pathways or redirect flux toward non-natural products. The space of possible metabolic solution can be further increased through approaches including 'new enzyme reactions', which are engineered on the basis of known enzyme mechanisms. Finally, by considering completely 'novel enzyme chemistries' with de novo enzyme design, the limits of nature can be breached to derive the most advanced form of synthetic pathways. We discuss the challenges and promises associated with these different metabolic engineering approaches and illuminate how enzyme engineering is expected to take a prime role in synthetic metabolic engineering for biotechnology, chemical industry and agriculture of the future.

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