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Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid
Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol deh...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003104/ https://www.ncbi.nlm.nih.gov/pubmed/29424954 http://dx.doi.org/10.1002/cbic.201700621 |
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author | Stavrinides, Anna K. Tatsis, Evangelos C. Dang, Thu‐Thuy Caputi, Lorenzo Stevenson, Clare E. M. Lawson, David M. Schneider, Bernd O'Connor, Sarah E. |
author_facet | Stavrinides, Anna K. Tatsis, Evangelos C. Dang, Thu‐Thuy Caputi, Lorenzo Stevenson, Clare E. M. Lawson, David M. Schneider, Bernd O'Connor, Sarah E. |
author_sort | Stavrinides, Anna K. |
collection | PubMed |
description | Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches. |
format | Online Article Text |
id | pubmed-6003104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60031042018-06-21 Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid Stavrinides, Anna K. Tatsis, Evangelos C. Dang, Thu‐Thuy Caputi, Lorenzo Stevenson, Clare E. M. Lawson, David M. Schneider, Bernd O'Connor, Sarah E. Chembiochem Full Papers Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches. John Wiley and Sons Inc. 2018-03-22 2018-05-04 /pmc/articles/PMC6003104/ /pubmed/29424954 http://dx.doi.org/10.1002/cbic.201700621 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Stavrinides, Anna K. Tatsis, Evangelos C. Dang, Thu‐Thuy Caputi, Lorenzo Stevenson, Clare E. M. Lawson, David M. Schneider, Bernd O'Connor, Sarah E. Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title | Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title_full | Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title_fullStr | Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title_full_unstemmed | Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title_short | Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid |
title_sort | discovery of a short‐chain dehydrogenase from catharanthus roseus that produces a new monoterpene indole alkaloid |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003104/ https://www.ncbi.nlm.nih.gov/pubmed/29424954 http://dx.doi.org/10.1002/cbic.201700621 |
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