Loading…
Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus
Summary 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 t...
Saved in:
Published in: | The Plant journal : for cell and molecular biology 2018-03, Vol.93 (5), p.943-958 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183 |
---|---|
cites | cdi_FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183 |
container_end_page | 958 |
container_issue | 5 |
container_start_page | 943 |
container_title | The Plant journal : for cell and molecular biology |
container_volume | 93 |
creator | Heskes, Allison M. Sundram, Tamil C.M. Boughton, Berin A. Jensen, Niels B. Hansen, Nikolaj L. Crocoll, Christoph Cozzi, Federico Rasmussen, Simon Hamberger, Britta Hamberger, Björn Staerk, Dan Møller, Birger L. Pateraki, Irini |
description | Summary
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.
Significance Statement
Furan and lactone diterpenoids of the medicinal plant, Vitex agnus‐castus, have received interest for their potential as new dopaminergic drugs. Through the application of MADLI‐MS imaging, targeted transcriptomics and enzyme functional characterisation, we report the identification of six diterpene synthases and a cytochrome P450, that in different combinations, catalyse steps towards their biosynthesis. |
doi_str_mv | 10.1111/tpj.13822 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5838521</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2002121031</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183</originalsourceid><addsrcrecordid>eNp1kctKxDAUhoMoOl4WvoAE3OiiM7k0SbsRdPCKoIiKu5CmqWboNLVp1dn5CD6jT2LGGUUFszmLfHz85_wAbGLUx-EN2nrUxzQhZAH0MOUsopjeLYIeSjmKRIzJClj1foQQFpTHy2CFpBSzlPIeuDqwzk-q9sF466ErYGad0q19MjC3rWlqUzmbe2grGBg4NrnVtlIlrEtVtfA2MC9Q3Vedf39908q3nV8HS4UqvdmYzzVwc3R4PTyJzi-OT4f755FmKCWRzqgheYJpnBOdZHkuNFWIMiYSwTMR00IViCERYK7ikFZlQqA85oHPME7oGtibeesuC7m0qdpGlbJu7Fg1E-mUlb9_Kvsg792TZAlNGMFBsDMXNO6xM76VY-u1KcNmxnVe4jRJGWMp4gHd_oOOXNeEO3hJECKYYESnwt0ZpRvnfWOK7zAYyWlTMjQlP5sK7NbP9N_kVzUBGMyAZ1uayf8meX15NlN-AMyynuA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2002121031</pqid></control><display><type>article</type><title>Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus</title><source>Wiley-Blackwell Read & Publish Collection</source><source>EZB Electronic Journals Library</source><creator>Heskes, Allison M. ; Sundram, Tamil C.M. ; Boughton, Berin A. ; Jensen, Niels B. ; Hansen, Nikolaj L. ; Crocoll, Christoph ; Cozzi, Federico ; Rasmussen, Simon ; Hamberger, Britta ; Hamberger, Björn ; Staerk, Dan ; Møller, Birger L. ; Pateraki, Irini</creator><creatorcontrib>Heskes, Allison M. ; Sundram, Tamil C.M. ; Boughton, Berin A. ; Jensen, Niels B. ; Hansen, Nikolaj L. ; Crocoll, Christoph ; Cozzi, Federico ; Rasmussen, Simon ; Hamberger, Britta ; Hamberger, Björn ; Staerk, Dan ; Møller, Birger L. ; Pateraki, Irini</creatorcontrib><description>Summary
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.
Significance Statement
Furan and lactone diterpenoids of the medicinal plant, Vitex agnus‐castus, have received interest for their potential as new dopaminergic drugs. Through the application of MADLI‐MS imaging, targeted transcriptomics and enzyme functional characterisation, we report the identification of six diterpene synthases and a cytochrome P450, that in different combinations, catalyse steps towards their biosynthesis.</description><identifier>ISSN: 0960-7412</identifier><identifier>EISSN: 1365-313X</identifier><identifier>DOI: 10.1111/tpj.13822</identifier><identifier>PMID: 29315936</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>bioactive diterpenoid ; Biological activity ; Biosynthesis ; Combinatorial analysis ; Cytochrome ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Cytochrome P450 ; Diterpenes ; Diterpenes - analysis ; Diterpenes - metabolism ; Dopamine ; Dopamine receptors ; Drugs ; Feature extraction ; Fungi ; Gene expression ; Gene Expression Profiling ; Herbal medicine ; Hydroxylation ; Ionization ; Lamiaceae ; Leaves ; MALDI‐MS imaging ; Mass spectrometry ; Mass spectroscopy ; Medicinal plants ; Menstruation ; Original ; Oxidation-Reduction ; Phylogeny ; Pituitary ; Pituitary gland ; Plant extracts ; Plant Leaves - genetics ; Plant Leaves - metabolism ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Plants, Medicinal - metabolism ; Prolactin ; Receptors ; Saccharomyces cerevisiae ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; terpene synthase ; Trichomes ; Trichomes - metabolism ; Vitex - genetics ; Vitex - metabolism ; Vitex agnus-castus</subject><ispartof>The Plant journal : for cell and molecular biology, 2018-03, Vol.93 (5), p.943-958</ispartof><rights>2018 The Authors published by John Wiley & Sons Ltd and Society for Experimental Biology.</rights><rights>2018 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.</rights><rights>Copyright © 2018 John Wiley & Sons Ltd and the Society for Experimental Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183</citedby><cites>FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29315936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heskes, Allison M.</creatorcontrib><creatorcontrib>Sundram, Tamil C.M.</creatorcontrib><creatorcontrib>Boughton, Berin A.</creatorcontrib><creatorcontrib>Jensen, Niels B.</creatorcontrib><creatorcontrib>Hansen, Nikolaj L.</creatorcontrib><creatorcontrib>Crocoll, Christoph</creatorcontrib><creatorcontrib>Cozzi, Federico</creatorcontrib><creatorcontrib>Rasmussen, Simon</creatorcontrib><creatorcontrib>Hamberger, Britta</creatorcontrib><creatorcontrib>Hamberger, Björn</creatorcontrib><creatorcontrib>Staerk, Dan</creatorcontrib><creatorcontrib>Møller, Birger L.</creatorcontrib><creatorcontrib>Pateraki, Irini</creatorcontrib><title>Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus</title><title>The Plant journal : for cell and molecular biology</title><addtitle>Plant J</addtitle><description>Summary
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.
Significance Statement
Furan and lactone diterpenoids of the medicinal plant, Vitex agnus‐castus, have received interest for their potential as new dopaminergic drugs. Through the application of MADLI‐MS imaging, targeted transcriptomics and enzyme functional characterisation, we report the identification of six diterpene synthases and a cytochrome P450, that in different combinations, catalyse steps towards their biosynthesis.</description><subject>bioactive diterpenoid</subject><subject>Biological activity</subject><subject>Biosynthesis</subject><subject>Combinatorial analysis</subject><subject>Cytochrome</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Cytochrome P450</subject><subject>Diterpenes</subject><subject>Diterpenes - analysis</subject><subject>Diterpenes - metabolism</subject><subject>Dopamine</subject><subject>Dopamine receptors</subject><subject>Drugs</subject><subject>Feature extraction</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Herbal medicine</subject><subject>Hydroxylation</subject><subject>Ionization</subject><subject>Lamiaceae</subject><subject>Leaves</subject><subject>MALDI‐MS imaging</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicinal plants</subject><subject>Menstruation</subject><subject>Original</subject><subject>Oxidation-Reduction</subject><subject>Phylogeny</subject><subject>Pituitary</subject><subject>Pituitary gland</subject><subject>Plant extracts</subject><subject>Plant Leaves - genetics</subject><subject>Plant Leaves - metabolism</subject><subject>Plant Proteins - genetics</subject><subject>Plant Proteins - metabolism</subject><subject>Plants, Medicinal - metabolism</subject><subject>Prolactin</subject><subject>Receptors</subject><subject>Saccharomyces cerevisiae</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>terpene synthase</subject><subject>Trichomes</subject><subject>Trichomes - metabolism</subject><subject>Vitex - genetics</subject><subject>Vitex - metabolism</subject><subject>Vitex agnus-castus</subject><issn>0960-7412</issn><issn>1365-313X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kctKxDAUhoMoOl4WvoAE3OiiM7k0SbsRdPCKoIiKu5CmqWboNLVp1dn5CD6jT2LGGUUFszmLfHz85_wAbGLUx-EN2nrUxzQhZAH0MOUsopjeLYIeSjmKRIzJClj1foQQFpTHy2CFpBSzlPIeuDqwzk-q9sF466ErYGad0q19MjC3rWlqUzmbe2grGBg4NrnVtlIlrEtVtfA2MC9Q3Vedf39908q3nV8HS4UqvdmYzzVwc3R4PTyJzi-OT4f755FmKCWRzqgheYJpnBOdZHkuNFWIMiYSwTMR00IViCERYK7ikFZlQqA85oHPME7oGtibeesuC7m0qdpGlbJu7Fg1E-mUlb9_Kvsg792TZAlNGMFBsDMXNO6xM76VY-u1KcNmxnVe4jRJGWMp4gHd_oOOXNeEO3hJECKYYESnwt0ZpRvnfWOK7zAYyWlTMjQlP5sK7NbP9N_kVzUBGMyAZ1uayf8meX15NlN-AMyynuA</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Heskes, Allison M.</creator><creator>Sundram, Tamil C.M.</creator><creator>Boughton, Berin A.</creator><creator>Jensen, Niels B.</creator><creator>Hansen, Nikolaj L.</creator><creator>Crocoll, Christoph</creator><creator>Cozzi, Federico</creator><creator>Rasmussen, Simon</creator><creator>Hamberger, Britta</creator><creator>Hamberger, Björn</creator><creator>Staerk, Dan</creator><creator>Møller, Birger L.</creator><creator>Pateraki, Irini</creator><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201803</creationdate><title>Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus</title><author>Heskes, Allison M. ; Sundram, Tamil C.M. ; Boughton, Berin A. ; Jensen, Niels B. ; Hansen, Nikolaj L. ; Crocoll, Christoph ; Cozzi, Federico ; Rasmussen, Simon ; Hamberger, Britta ; Hamberger, Björn ; Staerk, Dan ; Møller, Birger L. ; Pateraki, Irini</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>bioactive diterpenoid</topic><topic>Biological activity</topic><topic>Biosynthesis</topic><topic>Combinatorial analysis</topic><topic>Cytochrome</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Cytochrome P450</topic><topic>Diterpenes</topic><topic>Diterpenes - analysis</topic><topic>Diterpenes - metabolism</topic><topic>Dopamine</topic><topic>Dopamine receptors</topic><topic>Drugs</topic><topic>Feature extraction</topic><topic>Fungi</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Herbal medicine</topic><topic>Hydroxylation</topic><topic>Ionization</topic><topic>Lamiaceae</topic><topic>Leaves</topic><topic>MALDI‐MS imaging</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medicinal plants</topic><topic>Menstruation</topic><topic>Original</topic><topic>Oxidation-Reduction</topic><topic>Phylogeny</topic><topic>Pituitary</topic><topic>Pituitary gland</topic><topic>Plant extracts</topic><topic>Plant Leaves - genetics</topic><topic>Plant Leaves - metabolism</topic><topic>Plant Proteins - genetics</topic><topic>Plant Proteins - metabolism</topic><topic>Plants, Medicinal - metabolism</topic><topic>Prolactin</topic><topic>Receptors</topic><topic>Saccharomyces cerevisiae</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>terpene synthase</topic><topic>Trichomes</topic><topic>Trichomes - metabolism</topic><topic>Vitex - genetics</topic><topic>Vitex - metabolism</topic><topic>Vitex agnus-castus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heskes, Allison M.</creatorcontrib><creatorcontrib>Sundram, Tamil C.M.</creatorcontrib><creatorcontrib>Boughton, Berin A.</creatorcontrib><creatorcontrib>Jensen, Niels B.</creatorcontrib><creatorcontrib>Hansen, Nikolaj L.</creatorcontrib><creatorcontrib>Crocoll, Christoph</creatorcontrib><creatorcontrib>Cozzi, Federico</creatorcontrib><creatorcontrib>Rasmussen, Simon</creatorcontrib><creatorcontrib>Hamberger, Britta</creatorcontrib><creatorcontrib>Hamberger, Björn</creatorcontrib><creatorcontrib>Staerk, Dan</creatorcontrib><creatorcontrib>Møller, Birger L.</creatorcontrib><creatorcontrib>Pateraki, Irini</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Plant journal : for cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heskes, Allison M.</au><au>Sundram, Tamil C.M.</au><au>Boughton, Berin A.</au><au>Jensen, Niels B.</au><au>Hansen, Nikolaj L.</au><au>Crocoll, Christoph</au><au>Cozzi, Federico</au><au>Rasmussen, Simon</au><au>Hamberger, Britta</au><au>Hamberger, Björn</au><au>Staerk, Dan</au><au>Møller, Birger L.</au><au>Pateraki, Irini</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus</atitle><jtitle>The Plant journal : for cell and molecular biology</jtitle><addtitle>Plant J</addtitle><date>2018-03</date><risdate>2018</risdate><volume>93</volume><issue>5</issue><spage>943</spage><epage>958</epage><pages>943-958</pages><issn>0960-7412</issn><eissn>1365-313X</eissn><abstract>Summary
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.
Significance Statement
Furan and lactone diterpenoids of the medicinal plant, Vitex agnus‐castus, have received interest for their potential as new dopaminergic drugs. Through the application of MADLI‐MS imaging, targeted transcriptomics and enzyme functional characterisation, we report the identification of six diterpene synthases and a cytochrome P450, that in different combinations, catalyse steps towards their biosynthesis.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>29315936</pmid><doi>10.1111/tpj.13822</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0960-7412 |
ispartof | The Plant journal : for cell and molecular biology, 2018-03, Vol.93 (5), p.943-958 |
issn | 0960-7412 1365-313X |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5838521 |
source | Wiley-Blackwell Read & Publish Collection; EZB Electronic Journals Library |
subjects | bioactive diterpenoid Biological activity Biosynthesis Combinatorial analysis Cytochrome Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Cytochrome P450 Diterpenes Diterpenes - analysis Diterpenes - metabolism Dopamine Dopamine receptors Drugs Feature extraction Fungi Gene expression Gene Expression Profiling Herbal medicine Hydroxylation Ionization Lamiaceae Leaves MALDI‐MS imaging Mass spectrometry Mass spectroscopy Medicinal plants Menstruation Original Oxidation-Reduction Phylogeny Pituitary Pituitary gland Plant extracts Plant Leaves - genetics Plant Leaves - metabolism Plant Proteins - genetics Plant Proteins - metabolism Plants, Medicinal - metabolism Prolactin Receptors Saccharomyces cerevisiae Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization terpene synthase Trichomes Trichomes - metabolism Vitex - genetics Vitex - metabolism Vitex agnus-castus |
title | Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T17%3A13%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Biosynthesis%20of%20bioactive%20diterpenoids%20in%20the%20medicinal%20plant%20Vitex%20agnus%E2%80%90castus&rft.jtitle=The%20Plant%20journal%20:%20for%20cell%20and%20molecular%20biology&rft.au=Heskes,%20Allison%20M.&rft.date=2018-03&rft.volume=93&rft.issue=5&rft.spage=943&rft.epage=958&rft.pages=943-958&rft.issn=0960-7412&rft.eissn=1365-313X&rft_id=info:doi/10.1111/tpj.13822&rft_dat=%3Cproquest_pubme%3E2002121031%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5092-cb3e2d8134d2c8bdd7c3a03557876b743faf05075096a4593ab770d464d2b1183%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2002121031&rft_id=info:pmid/29315936&rfr_iscdi=true |