Retrosynthetic design of metabolic pathways to chemicals not found in nature
Biology produces a universe of chemicals whose precision and complexity is the envy of chemists. Over the last 30 years, the expansive field of metabolic engineering has many successes in optimizing the overproduction of metabolites of industrial interest, including moving natural product pathways t...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125854 |
| _version_ | 1826202047828983808 |
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| author | Lin, Geng-Min Warden-Rothman, Robert L Voigt, Christopher A. |
| author2 | Massachusetts Institute of Technology. Synthetic Biology Center |
| author_facet | Massachusetts Institute of Technology. Synthetic Biology Center Lin, Geng-Min Warden-Rothman, Robert L Voigt, Christopher A. |
| author_sort | Lin, Geng-Min |
| collection | MIT |
| description | Biology produces a universe of chemicals whose precision and complexity is the envy of chemists. Over the last 30 years, the expansive field of metabolic engineering has many successes in optimizing the overproduction of metabolites of industrial interest, including moving natural product pathways to production hosts (e.g., plants to yeast). However, there are stunningly few examples where enzymes are artificially combined to make a chemical that is not found somewhere in nature. Here, we review these efforts and discuss the challenges limiting the construction of such pathways. An analogy is made to the retrosynthesis problem solved in chemistry using algorithmic approaches, recently harnessing artificial intelligence, noting key differences in the needs of the optimization problem. When these issues are addressed, we see a future where chemistry and biology are intertwined in reaction networks that draw on the power of both to build currently unobtainable molecules across consumer, industrial, and defense applications. |
| first_indexed | 2024-09-23T12:01:22Z |
| format | Article |
| id | mit-1721.1/125854 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:01:22Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1258542022-10-01T07:40:08Z Retrosynthetic design of metabolic pathways to chemicals not found in nature Lin, Geng-Min Warden-Rothman, Robert L Voigt, Christopher A. Massachusetts Institute of Technology. Synthetic Biology Center Massachusetts Institute of Technology. Department of Biological Engineering Biology produces a universe of chemicals whose precision and complexity is the envy of chemists. Over the last 30 years, the expansive field of metabolic engineering has many successes in optimizing the overproduction of metabolites of industrial interest, including moving natural product pathways to production hosts (e.g., plants to yeast). However, there are stunningly few examples where enzymes are artificially combined to make a chemical that is not found somewhere in nature. Here, we review these efforts and discuss the challenges limiting the construction of such pathways. An analogy is made to the retrosynthesis problem solved in chemistry using algorithmic approaches, recently harnessing artificial intelligence, noting key differences in the needs of the optimization problem. When these issues are addressed, we see a future where chemistry and biology are intertwined in reaction networks that draw on the power of both to build currently unobtainable molecules across consumer, industrial, and defense applications. 2020-06-17T19:54:03Z 2020-06-17T19:54:03Z 2019-04 2020-03-18T13:53:20Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/125854 Lin, Geng-Min et al. "Retrosynthetic design of metabolic pathways to chemicals not found in nature." Biology 14 (April 2019): 82-107 © 2019 The Authors en http://dx.doi.org/10.1016/J.COISB.2019.04.004 Current Opinion in Systems Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Lin, Geng-Min Warden-Rothman, Robert L Voigt, Christopher A. Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title | Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title_full | Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title_fullStr | Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title_full_unstemmed | Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title_short | Retrosynthetic design of metabolic pathways to chemicals not found in nature |
| title_sort | retrosynthetic design of metabolic pathways to chemicals not found in nature |
| url | https://hdl.handle.net/1721.1/125854 |
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