The Reference Genome Sequence of Scutellaria baicalensis Provides Insights into the Evolution of Wogonin Biosynthesis.

Scutellaria baicalensis Georgi is important in Chinese Traditional Medicine where preparations of dried roots, 'Huang Qin'are used for liver and lung complaints including 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 9 pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence to those of closely related species in the order Lamiales, Sesamum indicum and Salvia splendens, revealed how the specialised metabolic pathway for the synthesis of 4'deoxyflavone bioactives evolved in the genus, Scutellaria. We found that the gene encoding a specific cinnamate CoA ligase likely obtained its new function following recent mutations, and 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 sub-functionalizations were involved in the evolution of 4'deoxyflavone synthesis in the genus, Scutellaria. The reference genome of S. baicalensis will facilitate the development of improved assemblies of genome sequences for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in members of the mint family, Lamiaceae, but also would facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants.