A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology
© 2018 American Chemical Society. Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances in technology, but it is difficult to ga...
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| Format: | Article |
| Jezik: | English |
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American Chemical Society (ACS)
2021
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| Online dostop: | https://hdl.handle.net/1721.1/133543 |
| _version_ | 1826201803220320256 |
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| author | Casini, Arturo Chang, Fang-Yuan Eluere, Raissa King, Andrew M Young, Eric M Dudley, Quentin M Karim, Ashty Pratt, Katelin Bristol, Cassandra Forget, Anthony Ghodasara, Amar Warden-Rothman, Robert Gan, Rui Cristofaro, Alexander Borujeni, Amin Espah Ryu, Min-Hyung Li, Jian Kwon, Yong-Chan Wang, He Tatsis, Evangelos Rodriguez-Lopez, Carlos O’Connor, Sarah Medema, Marnix H Fischbach, Michael A Jewett, Michael C Voigt, Christopher Gordon, D Benjamin |
| author_facet | Casini, Arturo Chang, Fang-Yuan Eluere, Raissa King, Andrew M Young, Eric M Dudley, Quentin M Karim, Ashty Pratt, Katelin Bristol, Cassandra Forget, Anthony Ghodasara, Amar Warden-Rothman, Robert Gan, Rui Cristofaro, Alexander Borujeni, Amin Espah Ryu, Min-Hyung Li, Jian Kwon, Yong-Chan Wang, He Tatsis, Evangelos Rodriguez-Lopez, Carlos O’Connor, Sarah Medema, Marnix H Fischbach, Michael A Jewett, Michael C Voigt, Christopher Gordon, D Benjamin |
| author_sort | Casini, Arturo |
| collection | MIT |
| description | © 2018 American Chemical Society. Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances in technology, but it is difficult to gauge current capabilities or identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", in which 3 months were given to build organisms to produce 10 molecules unknown to us in advance. By applying a diversity of new approaches, we produced the desired molecule or a closely related one for six out of 10 targets during the performance period and made advances toward production of the others as well. Specifically, we increased the titers of 1-hexadecanol, pyrrolnitrin, and pacidamycin D, found novel routes to the enediyne warhead underlying powerful antimicrobials, established a cell-free system for monoterpene production, produced an intermediate toward vincristine biosynthesis, and encoded 7802 individually retrievable pathways to 540 bisindoles in a DNA pool. Pathways to tetrahydrofuran and barbamide were designed and constructed, but toxicity or analytical tools inhibited further progress. In sum, we constructed 1.2 Mb DNA, built 215 strains spanning five species (Saccharomyces cerevisiae, Escherichia coli, Streptomyces albidoflavus, Streptomyces coelicolor, and Streptomyces albovinaceus), established two cell-free systems, and performed 690 assays developed in-house for the molecules. |
| first_indexed | 2024-09-23T11:57:28Z |
| format | Article |
| id | mit-1721.1/133543 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:57:28Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1335432022-03-29T20:51:32Z A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology Casini, Arturo Chang, Fang-Yuan Eluere, Raissa King, Andrew M Young, Eric M Dudley, Quentin M Karim, Ashty Pratt, Katelin Bristol, Cassandra Forget, Anthony Ghodasara, Amar Warden-Rothman, Robert Gan, Rui Cristofaro, Alexander Borujeni, Amin Espah Ryu, Min-Hyung Li, Jian Kwon, Yong-Chan Wang, He Tatsis, Evangelos Rodriguez-Lopez, Carlos O’Connor, Sarah Medema, Marnix H Fischbach, Michael A Jewett, Michael C Voigt, Christopher Gordon, D Benjamin © 2018 American Chemical Society. Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances in technology, but it is difficult to gauge current capabilities or identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", in which 3 months were given to build organisms to produce 10 molecules unknown to us in advance. By applying a diversity of new approaches, we produced the desired molecule or a closely related one for six out of 10 targets during the performance period and made advances toward production of the others as well. Specifically, we increased the titers of 1-hexadecanol, pyrrolnitrin, and pacidamycin D, found novel routes to the enediyne warhead underlying powerful antimicrobials, established a cell-free system for monoterpene production, produced an intermediate toward vincristine biosynthesis, and encoded 7802 individually retrievable pathways to 540 bisindoles in a DNA pool. Pathways to tetrahydrofuran and barbamide were designed and constructed, but toxicity or analytical tools inhibited further progress. In sum, we constructed 1.2 Mb DNA, built 215 strains spanning five species (Saccharomyces cerevisiae, Escherichia coli, Streptomyces albidoflavus, Streptomyces coelicolor, and Streptomyces albovinaceus), established two cell-free systems, and performed 690 assays developed in-house for the molecules. 2021-10-27T19:53:26Z 2021-10-27T19:53:26Z 2018 2019-09-19T12:24:24Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133543 en 10.1021/JACS.7B13292 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) Other repository |
| spellingShingle | Casini, Arturo Chang, Fang-Yuan Eluere, Raissa King, Andrew M Young, Eric M Dudley, Quentin M Karim, Ashty Pratt, Katelin Bristol, Cassandra Forget, Anthony Ghodasara, Amar Warden-Rothman, Robert Gan, Rui Cristofaro, Alexander Borujeni, Amin Espah Ryu, Min-Hyung Li, Jian Kwon, Yong-Chan Wang, He Tatsis, Evangelos Rodriguez-Lopez, Carlos O’Connor, Sarah Medema, Marnix H Fischbach, Michael A Jewett, Michael C Voigt, Christopher Gordon, D Benjamin A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title | A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title_full | A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title_fullStr | A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title_full_unstemmed | A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title_short | A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology |
| title_sort | pressure test to make 10 molecules in 90 days external evaluation of methods to engineer biology |
| url | https://hdl.handle.net/1721.1/133543 |
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