Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus

Vitex agnus‐castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ab...

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Main Authors:	Heskes, Allison M., Meenakshi Sundram, Tamil Chelvan, Boughton, Berin A., Jensen, Niels Bjerg, Hansen, Nikolaj Lervad, Crocoll, Christoph, Cozzi, Federico, Rasmussen, Silas Anselm, Hamberger, Britta, Hamberger, Björn Rn, Staerk, Dan, Lindberg Møller, Birger, Pateraki, Irini
Format:	Article
Language:	English English English
Published:	Blackwell Publishing Ltd 2018
Subjects:	Q Science (General)
Online Access:	http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/13/64055_Biosynthesis%20of%20bioactive%20diterpenoids_article.pdf http://irep.iium.edu.my/64055/2/64055_Biosynthesis%20of%20bioactive%20diterpenoids%20in%20the%20medicinal%20plant_scopus.pdf http://irep.iium.edu.my/64055/14/64055_Biosynthesis%20of%20bioactive%20diterpenoids_wos.pdf

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spelling	iium-640552019-08-31T01:29:29Z http://irep.iium.edu.my/64055/ Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus Heskes, Allison M. Meenakshi Sundram, Tamil Chelvan Boughton, Berin A. Jensen, Niels Bjerg Hansen, Nikolaj Lervad Crocoll, Christoph Cozzi, Federico Rasmussen, Silas Anselm Hamberger, Britta Hamberger, Björn Rn Staerk, Dan Lindberg Møller, Birger Pateraki, Irini Q Science (General) Vitex agnus‐castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus‐castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus‐castus. With the assistance of matrix‐assisted laser desorption ionisation‐mass spectrometry imaging (MALDI‐MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome‐specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus‐castus. The identified CYP, VacCYP76BK1, was found to catalyse 16‐hydroxylation of the diol‐diterpene, peregrinol, to labd‐13Z‐ene‐9,15,16‐triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan‐ and lactone‐containing diterpenoids that are present in this species. Blackwell Publishing Ltd 2018-03 Article PeerReviewed application/pdf en http://irep.iium.edu.my/64055/13/64055_Biosynthesis%20of%20bioactive%20diterpenoids_article.pdf application/pdf en http://irep.iium.edu.my/64055/2/64055_Biosynthesis%20of%20bioactive%20diterpenoids%20in%20the%20medicinal%20plant_scopus.pdf application/pdf en http://irep.iium.edu.my/64055/14/64055_Biosynthesis%20of%20bioactive%20diterpenoids_wos.pdf Heskes, Allison M. and Meenakshi Sundram, Tamil Chelvan and Boughton, Berin A. and Jensen, Niels Bjerg and Hansen, Nikolaj Lervad and Crocoll, Christoph and Cozzi, Federico and Rasmussen, Silas Anselm and Hamberger, Britta and Hamberger, Björn Rn and Staerk, Dan and Lindberg Møller, Birger and Pateraki, Irini (2018) Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus. Plant Journal, 93 (5). pp. 943-958. ISSN 0960-7412 E-ISSN 1365-313X https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838521/ 10.1111/tpj.13822
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	Q Science (General)
spellingShingle	Q Science (General) Heskes, Allison M. Meenakshi Sundram, Tamil Chelvan Boughton, Berin A. Jensen, Niels Bjerg Hansen, Nikolaj Lervad Crocoll, Christoph Cozzi, Federico Rasmussen, Silas Anselm Hamberger, Britta Hamberger, Björn Rn Staerk, Dan Lindberg Møller, Birger Pateraki, Irini Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
description	Vitex agnus‐castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus‐castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus‐castus. With the assistance of matrix‐assisted laser desorption ionisation‐mass spectrometry imaging (MALDI‐MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome‐specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus‐castus. The identified CYP, VacCYP76BK1, was found to catalyse 16‐hydroxylation of the diol‐diterpene, peregrinol, to labd‐13Z‐ene‐9,15,16‐triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan‐ and lactone‐containing diterpenoids that are present in this species.
format	Article
author	Heskes, Allison M. Meenakshi Sundram, Tamil Chelvan Boughton, Berin A. Jensen, Niels Bjerg Hansen, Nikolaj Lervad Crocoll, Christoph Cozzi, Federico Rasmussen, Silas Anselm Hamberger, Britta Hamberger, Björn Rn Staerk, Dan Lindberg Møller, Birger Pateraki, Irini
author_facet	Heskes, Allison M. Meenakshi Sundram, Tamil Chelvan Boughton, Berin A. Jensen, Niels Bjerg Hansen, Nikolaj Lervad Crocoll, Christoph Cozzi, Federico Rasmussen, Silas Anselm Hamberger, Britta Hamberger, Björn Rn Staerk, Dan Lindberg Møller, Birger Pateraki, Irini
author_sort	Heskes, Allison M.
title	Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
title_short	Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
title_full	Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
title_fullStr	Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
title_full_unstemmed	Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
title_sort	biosynthesis of bioactive diterpenoids in the medicinal plant vitex agnus-castus
publisher	Blackwell Publishing Ltd
publishDate	2018
url	http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/ http://irep.iium.edu.my/64055/13/64055_Biosynthesis%20of%20bioactive%20diterpenoids_article.pdf http://irep.iium.edu.my/64055/2/64055_Biosynthesis%20of%20bioactive%20diterpenoids%20in%20the%20medicinal%20plant_scopus.pdf http://irep.iium.edu.my/64055/14/64055_Biosynthesis%20of%20bioactive%20diterpenoids_wos.pdf
first_indexed	2023-09-18T21:30:51Z
last_indexed	2023-09-18T21:30:51Z
_version_	1777412500157890560

Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus

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