A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis

Sci Adv. 2016 Apr 8;2(4):e1501780. doi: 10.1126/sciadv.1501780. eCollection 2016 Apr.

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.

Keywords: Bioactive; Chinese Medicinal Plant; Flavone; Synthesis; Wogonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Biosynthetic Pathways / genetics
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Flavanones / biosynthesis*
  • Flavanones / chemistry
  • Flavones / biosynthesis*
  • Flavones / chemistry
  • Flavonoids / biosynthesis*
  • Flavonoids / chemistry
  • Gene Expression Regulation, Plant
  • Humans
  • Mice
  • Plant Extracts / chemistry
  • Plants, Medicinal / chemistry
  • Scutellaria baicalensis / chemistry

Substances

  • Antioxidants
  • Flavanones
  • Flavones
  • Flavonoids
  • Plant Extracts
  • Scutellaria baicalensis extract
  • baicalin
  • chrysin
  • Cytochrome P-450 Enzyme System
  • cytochrome P-450 CYP93B1 (Glycyrrhiza echinata)
  • Acyltransferases
  • flavanone synthetase
  • wogonin
  • flavone