Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis
Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human heal...
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| Veröffentlicht in: | Molecular plant 2018-01, Vol.11 (1), p.135-148 |
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| creator | Zhao, Qing Cui, Meng-Ying Levsh, Olesya Yang, Dongfeng Liu, Jie Li, Jie Hill, Lionel Yang, Lei Hu, Yonghong Weng, Jing-Ke Chen, Xiao-Ya Martin, Cathie |
| description | Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2. |
| doi_str_mv | 10.1016/j.molp.2017.08.009 |
| format | Article |
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These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.</description><identifier>ISSN: 1674-2052</identifier><identifier>EISSN: 1752-9867</identifier><identifier>DOI: 10.1016/j.molp.2017.08.009</identifier><identifier>PMID: 28842248</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>aerial parts ; antioxidants ; apigenin ; Apigenin - metabolism ; apoptosis ; baicalein ; baicalin ; bioactive compounds ; biosynthesis ; chrysin ; Cytochrome P-450 Enzyme System - metabolism ; enzymes ; Flavanones - metabolism ; flavone 6-hydroxylase ; flavone 8-hydroxylase ; Flavones - metabolism ; Flavonoids - metabolism ; gene duplication ; glycosides ; Huangqin ; Humans ; medicinal plants ; neoplasms ; Phylogeny ; Plant Roots - metabolism ; roots ; Saccharomyces cerevisiae - metabolism ; Scutellaria baicalensis ; Scutellaria baicalensis - genetics ; Scutellaria baicalensis - metabolism ; substrate specificity ; wogonin ; 黄酮;黄芩;合成;apoptosis;CYP450;酶;抗氧化剂;种系发生</subject><ispartof>Molecular plant, 2018-01, Vol.11 (1), p.135-148</ispartof><rights>2017 The Authors</rights><rights>Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2017 The Authors 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-d7f621f0bf5f1f23394dd72e4d037b27939a1abb51dc916a522b54bcf31c647a3</citedby><cites>FETCH-LOGICAL-c515t-d7f621f0bf5f1f23394dd72e4d037b27939a1abb51dc916a522b54bcf31c647a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/90143B/90143B.jpg</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28842248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Qing</creatorcontrib><creatorcontrib>Cui, Meng-Ying</creatorcontrib><creatorcontrib>Levsh, Olesya</creatorcontrib><creatorcontrib>Yang, Dongfeng</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Hill, Lionel</creatorcontrib><creatorcontrib>Yang, Lei</creatorcontrib><creatorcontrib>Hu, Yonghong</creatorcontrib><creatorcontrib>Weng, Jing-Ke</creatorcontrib><creatorcontrib>Chen, Xiao-Ya</creatorcontrib><creatorcontrib>Martin, Cathie</creatorcontrib><title>Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis</title><title>Molecular plant</title><addtitle>Molecular Plant</addtitle><description>Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.</description><subject>aerial parts</subject><subject>antioxidants</subject><subject>apigenin</subject><subject>Apigenin - metabolism</subject><subject>apoptosis</subject><subject>baicalein</subject><subject>baicalin</subject><subject>bioactive compounds</subject><subject>biosynthesis</subject><subject>chrysin</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>enzymes</subject><subject>Flavanones - metabolism</subject><subject>flavone 6-hydroxylase</subject><subject>flavone 8-hydroxylase</subject><subject>Flavones - metabolism</subject><subject>Flavonoids - metabolism</subject><subject>gene duplication</subject><subject>glycosides</subject><subject>Huangqin</subject><subject>Humans</subject><subject>medicinal plants</subject><subject>neoplasms</subject><subject>Phylogeny</subject><subject>Plant Roots - metabolism</subject><subject>roots</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Scutellaria baicalensis</subject><subject>Scutellaria baicalensis - genetics</subject><subject>Scutellaria baicalensis - metabolism</subject><subject>substrate specificity</subject><subject>wogonin</subject><subject>黄酮;黄芩;合成;apoptosis;CYP450;酶;抗氧化剂;种系发生</subject><issn>1674-2052</issn><issn>1752-9867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEoqXwAiyQxYpNgn_i2JYQUpm2FKkSiJYFK8tx7BmPMvbUTgbCA8BL8U68Ah5mGMEGVr6Sv3N87z0uiscIVgii5vmyWoV-XWGIWAV5BaG4UxwjRnEpeMPu5rphdYkhxUfFg5SWEDaQN-R-cYQ5rzGu-XHx9eZTALOP7zg-A-f-y7QyCVyMXg8ueKBy3atN8AZcTl0Mn6depQw4D4aFAa9cSJPPVXIJBAvehzCU12ujnXUa1D--fyvPTBbZnccv3bUeB9P3KjoFWuW06o3P8ofFPav6ZB7tz5Piw8X5zeyyvHr7-s3s9KrUFNGh7JhtMLKwtdQiiwkRddcxbOoOEtZiJohQSLUtRZ0WqFEU45bWrbYE6aZmipwUL3e-67FdmU4bP0TVy3V0KxUnGZSTf994t5DzsJGUMYgEzwbP9gYx3I4mDXLlkt5O5E0Yk8QQQlqLhuP_okgQzIkgkGUU71AdQ0rR2ENHCMpt1nIpt1nLbdYScpmzzqInf85ykPwONwMvdoDJG904E2XSznhtOheNHmQX3L_9n-6bWgQ_v3V-fngi_ytGKOOc_ASbh8oN</recordid><startdate>20180108</startdate><enddate>20180108</enddate><creator>Zhao, Qing</creator><creator>Cui, Meng-Ying</creator><creator>Levsh, Olesya</creator><creator>Yang, Dongfeng</creator><creator>Liu, Jie</creator><creator>Li, Jie</creator><creator>Hill, Lionel</creator><creator>Yang, Lei</creator><creator>Hu, Yonghong</creator><creator>Weng, Jing-Ke</creator><creator>Chen, Xiao-Ya</creator><creator>Martin, Cathie</creator><general>Elsevier Inc</general><general>Oxford University Press</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W94</scope><scope>WU4</scope><scope>~WA</scope><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20180108</creationdate><title>Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis</title><author>Zhao, Qing ; Cui, Meng-Ying ; Levsh, Olesya ; Yang, Dongfeng ; Liu, Jie ; Li, Jie ; Hill, Lionel ; Yang, Lei ; Hu, Yonghong ; Weng, Jing-Ke ; Chen, Xiao-Ya ; Martin, Cathie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-d7f621f0bf5f1f23394dd72e4d037b27939a1abb51dc916a522b54bcf31c647a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>aerial parts</topic><topic>antioxidants</topic><topic>apigenin</topic><topic>Apigenin - metabolism</topic><topic>apoptosis</topic><topic>baicalein</topic><topic>baicalin</topic><topic>bioactive compounds</topic><topic>biosynthesis</topic><topic>chrysin</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>enzymes</topic><topic>Flavanones - metabolism</topic><topic>flavone 6-hydroxylase</topic><topic>flavone 8-hydroxylase</topic><topic>Flavones - metabolism</topic><topic>Flavonoids - metabolism</topic><topic>gene duplication</topic><topic>glycosides</topic><topic>Huangqin</topic><topic>Humans</topic><topic>medicinal plants</topic><topic>neoplasms</topic><topic>Phylogeny</topic><topic>Plant Roots - metabolism</topic><topic>roots</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Scutellaria baicalensis</topic><topic>Scutellaria baicalensis - genetics</topic><topic>Scutellaria baicalensis - metabolism</topic><topic>substrate specificity</topic><topic>wogonin</topic><topic>黄酮;黄芩;合成;apoptosis;CYP450;酶;抗氧化剂;种系发生</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Qing</creatorcontrib><creatorcontrib>Cui, Meng-Ying</creatorcontrib><creatorcontrib>Levsh, Olesya</creatorcontrib><creatorcontrib>Yang, Dongfeng</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Hill, Lionel</creatorcontrib><creatorcontrib>Yang, Lei</creatorcontrib><creatorcontrib>Hu, Yonghong</creatorcontrib><creatorcontrib>Weng, Jing-Ke</creatorcontrib><creatorcontrib>Chen, Xiao-Ya</creatorcontrib><creatorcontrib>Martin, Cathie</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-自然科学</collection><collection>中文科技期刊数据库-自然科学-生物科学</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular plant</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Qing</au><au>Cui, Meng-Ying</au><au>Levsh, Olesya</au><au>Yang, Dongfeng</au><au>Liu, Jie</au><au>Li, Jie</au><au>Hill, Lionel</au><au>Yang, Lei</au><au>Hu, Yonghong</au><au>Weng, Jing-Ke</au><au>Chen, Xiao-Ya</au><au>Martin, Cathie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis</atitle><jtitle>Molecular plant</jtitle><addtitle>Molecular Plant</addtitle><date>2018-01-08</date><risdate>2018</risdate><volume>11</volume><issue>1</issue><spage>135</spage><epage>148</epage><pages>135-148</pages><issn>1674-2052</issn><eissn>1752-9867</eissn><abstract>Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>28842248</pmid><doi>10.1016/j.molp.2017.08.009</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | aerial parts antioxidants apigenin Apigenin - metabolism apoptosis baicalein baicalin bioactive compounds biosynthesis chrysin Cytochrome P-450 Enzyme System - metabolism enzymes Flavanones - metabolism flavone 6-hydroxylase flavone 8-hydroxylase Flavones - metabolism Flavonoids - metabolism gene duplication glycosides Huangqin Humans medicinal plants neoplasms Phylogeny Plant Roots - metabolism roots Saccharomyces cerevisiae - metabolism Scutellaria baicalensis Scutellaria baicalensis - genetics Scutellaria baicalensis - metabolism substrate specificity wogonin 黄酮 黄芩 合成 apoptosis CYP450 酶 抗氧化剂 种系发生 |
| title | Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis |
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