A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
Abstract Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in indus...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47387-1 |
| _version_ | 1797209216388169728 |
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| author | Kevin B. Reed Sierra M. Brooks Jordan Wells Kristin J. Blake Minye Zhao Kira Placido Simon d’Oelsnitz Adit Trivedi Shruti Gadhiyar Hal S. Alper |
| author_facet | Kevin B. Reed Sierra M. Brooks Jordan Wells Kristin J. Blake Minye Zhao Kira Placido Simon d’Oelsnitz Adit Trivedi Shruti Gadhiyar Hal S. Alper |
| author_sort | Kevin B. Reed |
| collection | DOAJ |
| description | Abstract Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose. First, we engineer E. coli to produce between 300 and 700 mg/L of six different halogenated tryptophan precursors. Second, we harness the native promiscuity of multiple downstream enzymes to access unexplored regions of metabolism. Finally, through modular co-culture fermentations, we demonstrate a plug-and-play bioproduction platform, culminating in the generation of 26 distinct halogenated molecules produced de novo including precursors to prodrugs 4-chloro- and 4-bromo-kynurenine and new-to-nature halogenated beta carbolines. |
| first_indexed | 2024-04-24T09:51:10Z |
| format | Article |
| id | doaj.art-8260c887a6ec49b9968a8f5117e7e310 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T09:51:10Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8260c887a6ec49b9968a8f5117e7e3102024-04-14T11:22:02ZengNature PortfolioNature Communications2041-17232024-04-0115111310.1038/s41467-024-47387-1A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived moleculesKevin B. Reed0Sierra M. Brooks1Jordan Wells2Kristin J. Blake3Minye Zhao4Kira Placido5Simon d’Oelsnitz6Adit Trivedi7Shruti Gadhiyar8Hal S. Alper9McKetta Department of Chemical Engineering, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinMass Spectrometry Facility, Department of Chemistry, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinInstitute for Cellular and Molecular Biology, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinMcKetta Department of Chemical Engineering, The University of Texas at AustinAbstract Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose. First, we engineer E. coli to produce between 300 and 700 mg/L of six different halogenated tryptophan precursors. Second, we harness the native promiscuity of multiple downstream enzymes to access unexplored regions of metabolism. Finally, through modular co-culture fermentations, we demonstrate a plug-and-play bioproduction platform, culminating in the generation of 26 distinct halogenated molecules produced de novo including precursors to prodrugs 4-chloro- and 4-bromo-kynurenine and new-to-nature halogenated beta carbolines.https://doi.org/10.1038/s41467-024-47387-1 |
| spellingShingle | Kevin B. Reed Sierra M. Brooks Jordan Wells Kristin J. Blake Minye Zhao Kira Placido Simon d’Oelsnitz Adit Trivedi Shruti Gadhiyar Hal S. Alper A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules Nature Communications |
| title | A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules |
| title_full | A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules |
| title_fullStr | A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules |
| title_full_unstemmed | A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules |
| title_short | A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules |
| title_sort | modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan derived molecules |
| url | https://doi.org/10.1038/s41467-024-47387-1 |
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