Dear Editor,Leonurus japonicus(L.japonicus,Chinese motherwort)(Figure 1A),a staple in traditional medicine and officially listed in the Chinese Pharmacopoeia,is notable within the Lamiaceae family.While most species i...Dear Editor,Leonurus japonicus(L.japonicus,Chinese motherwort)(Figure 1A),a staple in traditional medicine and officially listed in the Chinese Pharmacopoeia,is notable within the Lamiaceae family.While most species in this family produce terpenoids as primary bioactive compounds,L.japonicus accumulates high levels of alkaloids.Stachydrine and leonurine serve as its main chemical markers and active medicinal ingredients,with stachydrine concentrations nearly 10-fold higher than those of leonurine.展开更多
Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We re...Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408.14-Mb genome has been assembled into nine pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence with those of closely related species in the order Lamiales, sesamum indicum and Salvia splendens,revealed that a specialized metabolic pathway for the synthesis of 4'-deoxyflavone bioactives evolved in the genus Scu-tellaria. We found that the gene encoding a specific cinnamate coenzyme A ligase likely obtained its newfunc- tion following recent mutations, and that four genes encoding enzymes in the 4'-deoxyflavone pathway are present as tandem repeats in the genome of S. baicalensis. Further analyses revealed that gene duplications, segmental duplication, gene amplification, and point mutations coupled to gene neo- and subfunctionaliza-tions were involved in the evolution of 4'-deoxyflavone synthesis in the genus Scutellaria. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants. The reference genome of S. baicalensis is also useful for improving the genome assemblies for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants.展开更多
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 eff...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.展开更多
基金supported by the Shanghai Agricultural Science and Technology Innovation Project(T2024215 to P.X.)the Chenshan Special Fund for the Shanghai Landscaping Administration Bureau Program(G232402 to P.X.)the Science and Technology Commission of Shanghai Municipality(YDZX20223100001003 and YDZX20243100004002 to Y.-H.H.).
文摘Dear Editor,Leonurus japonicus(L.japonicus,Chinese motherwort)(Figure 1A),a staple in traditional medicine and officially listed in the Chinese Pharmacopoeia,is notable within the Lamiaceae family.While most species in this family produce terpenoids as primary bioactive compounds,L.japonicus accumulates high levels of alkaloids.Stachydrine and leonurine serve as its main chemical markers and active medicinal ingredients,with stachydrine concentrations nearly 10-fold higher than those of leonurine.
基金National Key R&D Program of China (2018YFC1706200,2018YFD1000701-4)the National Natural Science Foundation of China (31870282, 31700268 and 31788103)+2 种基金the Fund of Chinese Academy of Sciences (QYZDY-SSW-SMC026 and 153D31KYSB20160074)the Chenshan Special Fund for Shanghai Landscaping Administration Bureau Program (G182401, G172402, G182402, G192413, and G192414)the CAS/JIC and Center of Excellence for Plant and Microbial Sciences (CEPAMS) joint foundation through support to Q.Z., X.Y.C., J.Y., and C.M. Q.Z. and J.Y. were also supported by the Youth Innovation Promotion Association, Chinese Academy of Sciences.
文摘Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408.14-Mb genome has been assembled into nine pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence with those of closely related species in the order Lamiales, sesamum indicum and Salvia splendens,revealed that a specialized metabolic pathway for the synthesis of 4'-deoxyflavone bioactives evolved in the genus Scu-tellaria. We found that the gene encoding a specific cinnamate coenzyme A ligase likely obtained its newfunc- tion following recent mutations, and that four genes encoding enzymes in the 4'-deoxyflavone pathway are present as tandem repeats in the genome of S. baicalensis. Further analyses revealed that gene duplications, segmental duplication, gene amplification, and point mutations coupled to gene neo- and subfunctionaliza-tions were involved in the evolution of 4'-deoxyflavone synthesis in the genus Scutellaria. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants. The reference genome of S. baicalensis is also useful for improving the genome assemblies for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants.
文摘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.
