Directed Biosynthesis of Mitragynine Stereoisomers

[Image: see text] Mitragyna speciosa (“kratom”) is used as a natural remedy for pain and management of opioid dependence. The pharmacological properties of kratom have been linked to a complex mixture of monoterpene indole alkaloids, most notably mitragynine. Here, we report the central biosynthetic...

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Autores principales: Schotte, Carsten, Jiang, Yindi, Grzech, Dagny, Dang, Thu-Thuy T., Laforest, Larissa C., León, Francisco, Mottinelli, Marco, Nadakuduti, Satya Swathi, McCurdy, Christopher R., O’Connor, Sarah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999412/
https://www.ncbi.nlm.nih.gov/pubmed/36883326
http://dx.doi.org/10.1021/jacs.2c13644
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author Schotte, Carsten
Jiang, Yindi
Grzech, Dagny
Dang, Thu-Thuy T.
Laforest, Larissa C.
León, Francisco
Mottinelli, Marco
Nadakuduti, Satya Swathi
McCurdy, Christopher R.
O’Connor, Sarah E.
author_facet Schotte, Carsten
Jiang, Yindi
Grzech, Dagny
Dang, Thu-Thuy T.
Laforest, Larissa C.
León, Francisco
Mottinelli, Marco
Nadakuduti, Satya Swathi
McCurdy, Christopher R.
O’Connor, Sarah E.
author_sort Schotte, Carsten
collection PubMed
description [Image: see text] Mitragyna speciosa (“kratom”) is used as a natural remedy for pain and management of opioid dependence. The pharmacological properties of kratom have been linked to a complex mixture of monoterpene indole alkaloids, most notably mitragynine. Here, we report the central biosynthetic steps responsible for the scaffold formation of mitragynine and related corynanthe-type alkaloids. We illuminate the mechanistic basis by which the key stereogenic center of this scaffold is formed. These discoveries were leveraged for the enzymatic production of mitragynine, the C-20 epimer speciogynine, and fluorinated analogues.
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spelling pubmed-99994122023-03-11 Directed Biosynthesis of Mitragynine Stereoisomers Schotte, Carsten Jiang, Yindi Grzech, Dagny Dang, Thu-Thuy T. Laforest, Larissa C. León, Francisco Mottinelli, Marco Nadakuduti, Satya Swathi McCurdy, Christopher R. O’Connor, Sarah E. J Am Chem Soc [Image: see text] Mitragyna speciosa (“kratom”) is used as a natural remedy for pain and management of opioid dependence. The pharmacological properties of kratom have been linked to a complex mixture of monoterpene indole alkaloids, most notably mitragynine. Here, we report the central biosynthetic steps responsible for the scaffold formation of mitragynine and related corynanthe-type alkaloids. We illuminate the mechanistic basis by which the key stereogenic center of this scaffold is formed. These discoveries were leveraged for the enzymatic production of mitragynine, the C-20 epimer speciogynine, and fluorinated analogues. American Chemical Society 2023-02-22 /pmc/articles/PMC9999412/ /pubmed/36883326 http://dx.doi.org/10.1021/jacs.2c13644 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Schotte, Carsten
Jiang, Yindi
Grzech, Dagny
Dang, Thu-Thuy T.
Laforest, Larissa C.
León, Francisco
Mottinelli, Marco
Nadakuduti, Satya Swathi
McCurdy, Christopher R.
O’Connor, Sarah E.
Directed Biosynthesis of Mitragynine Stereoisomers
title Directed Biosynthesis of Mitragynine Stereoisomers
title_full Directed Biosynthesis of Mitragynine Stereoisomers
title_fullStr Directed Biosynthesis of Mitragynine Stereoisomers
title_full_unstemmed Directed Biosynthesis of Mitragynine Stereoisomers
title_short Directed Biosynthesis of Mitragynine Stereoisomers
title_sort directed biosynthesis of mitragynine stereoisomers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999412/
https://www.ncbi.nlm.nih.gov/pubmed/36883326
http://dx.doi.org/10.1021/jacs.2c13644
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