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...
| Glavni autori: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Članak |
| Jezik: | English |
| Izdano: |
American Chemical Society (ACS)
2021
|
| Online pristup: | https://hdl.handle.net/1721.1/133543 |
| _version_ | 1826201803220320256 |
|---|---|
| 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 |
| work_keys_str_mv | AT casiniarturo apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT changfangyuan apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT eluereraissa apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT kingandrewm apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT youngericm apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT dudleyquentinm apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT karimashty apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT prattkatelin apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT bristolcassandra apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT forgetanthony apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ghodasaraamar apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT wardenrothmanrobert apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ganrui apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT cristofaroalexander apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT borujeniaminespah apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ryuminhyung apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT lijian apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT kwonyongchan apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT wanghe apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT tatsisevangelos apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT rodriguezlopezcarlos apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT oconnorsarah apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT medemamarnixh apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT fischbachmichaela apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT jewettmichaelc apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT voigtchristopher apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT gordondbenjamin apressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT casiniarturo pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT changfangyuan pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT eluereraissa pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT kingandrewm pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT youngericm pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT dudleyquentinm pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT karimashty pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT prattkatelin pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT bristolcassandra pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT forgetanthony pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ghodasaraamar pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT wardenrothmanrobert pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ganrui pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT cristofaroalexander pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT borujeniaminespah pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT ryuminhyung pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT lijian pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT kwonyongchan pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT wanghe pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT tatsisevangelos pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT rodriguezlopezcarlos pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT oconnorsarah pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT medemamarnixh pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT fischbachmichaela pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT jewettmichaelc pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT voigtchristopher pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology AT gordondbenjamin pressuretesttomake10moleculesin90daysexternalevaluationofmethodstoengineerbiology |