title: A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis.
abstract: Wogonin and baicalein are bioactive flavones in the popular Chinese herbal remedy Huang-Qin (Scutellaria baicalensis Georgi). These specialized flavones lack a 4'-hydroxyl group on the B ring (4'-deoxyflavones) and induce apoptosis in a wide spectrum of human tumor cells in vitro and inhibit tumor growth in vivo in different mouse tumor models. Root-specific flavones (RSFs) from Scutellaria have a variety of reported additional beneficial effects including antioxidant and antiviral properties. We describe the characterization of a new pathway for the synthesis of these compounds, in which pinocembrin (a 4'-deoxyflavanone) serves as a key intermediate. Although two genes encoding flavone synthase II (FNSII) are expressed in the roots of S. baicalensis, FNSII-1 has broad specificity for flavanones as substrates, whereas FNSII-2 is specific for pinocembrin. FNSII-2 is responsible for the synthesis of 4'-deoxyRSFs, such as chrysin and wogonin, wogonoside, baicalein, and baicalin, which are synthesized from chrysin. A gene encoding a cinnamic acid-specific coenzyme A ligase (SbCLL-7), which is highly expressed in roots, is required for the synthesis of RSFs by FNSII-2, as demonstrated by gene silencing. A specific isoform of chalcone synthase (SbCHS-2) that is highly expressed in roots producing RSFs is also required for the synthesis of chrysin. Our studies reveal a recently evolved pathway for biosynthesis of specific, bioactive 4'-deoxyflavones in the roots of S. baicalensis.
authors.affiliation: Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200032, China.; Department of Metabolic Biology, John Innes Centre (JIC), Norwich NR4 7UH, UK.; School of Environmental Science and Engineering, Tianjin University, Tianjin 300072, China.; CAS-JIC Centre of Excellence for Plant and Microbial Sciences, 300 Feng Lin Road, Shanghai 200032, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Metabolic Biology, John Innes Centre (JIC), Norwich NR4 7UH, UK.
authors.forename: Yang
authors.identifier: 0000-0002-7793-1108
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Environmental Science and Engineering, Tianjin University, Tianjin 300072, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Metabolic Biology, John Innes Centre (JIC), Norwich NR4 7UH, UK.
authors.forename: Lionel
authors.initials: L
authors.lastname: Hill
authors.affiliation: Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Jing-Ke
authors.identifier: 0000-0003-3059-0075
authors.initials: JK
authors.lastname: Weng
authors.affiliation: Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200032, China.; CAS-JIC Centre of Excellence for Plant and Microbial Sciences, 300 Feng Lin Road, Shanghai 200032, China.; Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai Chenshan Botanical Garden, Shanghai 201602, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200032, China.; CAS-JIC Centre of Excellence for Plant and Microbial Sciences, 300 Feng Lin Road, Shanghai 200032, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Metabolic Biology, John Innes Centre (JIC), Norwich NR4 7UH, UK.; CAS-JIC Centre of Excellence for Plant and Microbial Sciences, 300 Feng Lin Road, Shanghai 200032, China.
authors.forename: Cathie
authors.identifier: 0000-0002-3640-5080
authors.initials: C
authors.lastname: Martin
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053898:Biosynthetic Pathways / Q000235:genetics; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000096:biosynthesis* / Q000737:chemistry; D047309:Flavones / Q000096:biosynthesis* / Q000737:chemistry; D005419:Flavonoids / Q000096:biosynthesis* / Q000737:chemistry; D018506:Gene Expression Regulation, Plant; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D031364:Scutellaria baicalensis / Q000737:chemistry
chemical_list: D000975:Antioxidants; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract; C038044:baicalin; C043561:chrysin; D003577:Cytochrome P-450 Enzyme System; C114032:cytochrome P-450 CYP93B1 (Glycyrrhiza echinata); D000217:Acyltransferases; C020141:flavanone synthetase; C085514:wogonin; C043562:flavone
keywords: Bioactive; Chinese Medicinal Plant; Flavone; Synthesis; Wogonin