Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis
Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show th...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96361 |
| _version_ | 1826195896461688832 |
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| author | Lee, Hyang-Yeol Yerkes, Nancy Mary O'Connor, Sarah Ellen Yerkes, Nancy Mary |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Lee, Hyang-Yeol Yerkes, Nancy Mary O'Connor, Sarah Ellen Yerkes, Nancy Mary |
| author_sort | Lee, Hyang-Yeol |
| collection | MIT |
| description | Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways. |
| first_indexed | 2024-09-23T10:17:33Z |
| format | Article |
| id | mit-1721.1/96361 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:17:33Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/963612022-09-26T17:01:10Z Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis Lee, Hyang-Yeol Yerkes, Nancy Mary O'Connor, Sarah Ellen Yerkes, Nancy Mary Massachusetts Institute of Technology. Department of Chemistry Lee, Hyang-Yeol Yerkes, Nancy Mary O'Connor, Sarah Ellen Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways. National Institutes of Health (U.S.) (grant NIH GM074820) 2015-04-02T20:01:02Z 2015-04-02T20:01:02Z 2009-12 2009-10 Article http://purl.org/eprint/type/JournalArticle 10745521 http://hdl.handle.net/1721.1/96361 Lee, Hyang-Yeol, Nancy Yerkes, and Sarah E. O’Connor. “Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis.” Chemistry & Biology 16, no. 12 (December 2009): 1225–1229. © 2009 Elsevier Ltd. en_US http://dx.doi.org/10.1016/j.chembiol.2009.11.016 Chemistry & Biology 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 Elsevier B.V. Elsevier |
| spellingShingle | Lee, Hyang-Yeol Yerkes, Nancy Mary O'Connor, Sarah Ellen Yerkes, Nancy Mary Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title | Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title_full | Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title_fullStr | Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title_full_unstemmed | Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title_short | Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis |
| title_sort | aza tryptamine substrates in monoterpene indole alkaloid biosynthesis |
| url | http://hdl.handle.net/1721.1/96361 |
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