The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown....The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown.Here,we report a high-quality assembly of the 414.98 Mb genome of S.barbata into 13 pseudochromosomes.Using phylogenomic and biochemical data,we mapped the plastidial metabolism of kaurene(gibberellins),abietane,and clerodane diterpenes in three species of the family Lamiaceae(Scutellaria barbata,Scutellaria baicalensis,and Salvia splendens),facilitating the identification of genes involved in the biosynthesis of the clerodanes,kolavenol,and isokolavenol.We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism.Despite the assumed monophyletic origin of clerodane biosynthesis,which is widespread in species of the Lamiaceae,our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae.Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family,Lamiaceae,but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.展开更多
基金the Royal Society for the Newton Advanced Fellowship awarded to E.C.T.(NAF\R2\192001)and CEPAMS Funding(Project CPM19)for support of the collaboration project‘‘Scutellaria Anticancer Metabolites’’for C.M.and E.C.T.C.M.was also supported by the Institute Strategic Programme‘‘Molecules from Nature’’(BB/P012523/1)from the UK Biotechnology and Biological Sciences Research Council.E.C.T.was also supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB27020204)International Partnership Program of Chinese Academy of Sciences(153D31KYSB 20160074)Ministry of Science and Technology for Foreign Expert Project 2019(G20190113016),the Science and Technology Commission of Shanghai Municipality for Shanghai Talent Recruitment Programs.A.L.M.M.was supported by the CAS PIFI Fellowship and the China Postdoctoral Science Foundation for Postdoctoral International Exchange Program Fellowship.H.L.is supported by the National Natural Science Foundation of China through Young Scientists Fund(32200313).
文摘The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown.Here,we report a high-quality assembly of the 414.98 Mb genome of S.barbata into 13 pseudochromosomes.Using phylogenomic and biochemical data,we mapped the plastidial metabolism of kaurene(gibberellins),abietane,and clerodane diterpenes in three species of the family Lamiaceae(Scutellaria barbata,Scutellaria baicalensis,and Salvia splendens),facilitating the identification of genes involved in the biosynthesis of the clerodanes,kolavenol,and isokolavenol.We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism.Despite the assumed monophyletic origin of clerodane biosynthesis,which is widespread in species of the Lamiaceae,our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae.Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family,Lamiaceae,but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.