The discovery of novel flavonoids and elucidation of their biosynthesis are fundamental to understanding their roles in plants and their benefits for human and animal health.Here,we report a new pathway for polymeriza...The discovery of novel flavonoids and elucidation of their biosynthesis are fundamental to understanding their roles in plants and their benefits for human and animal health.Here,we report a new pathway for polymerization of a group of novel oligomeric flavonoids in plants.We engineered red cells for discovering genes of interest involved in the flavonoid pathway and identified a gene encoding a novel flavanol polymerase(FP)localized in the central vacuole.FP catalyzes the polymerization of flavanols,such as epicatechin and catechin,to produce yellowish dimers or oligomers.Structural elucidation shows that these compounds feature a novel oligomeric flaven–flavan(FF)skeleton linked by interflavan–flaven and interflaven bonds,distinguishing them from proanthocyanidins and dehydrodicatechins.Detailed chemical and physical characterizations further confirmed the novel FFs as flavonoids.Mechanistic investigations demonstrated that FP polymerizes flavan-3-ols and flav-2-en-3-ol carbocation,forming dimeric or oligomeric flaven-4→8-flavans,which we term“papanridins.”Data from transgenic experiments,mutant analysis,metabolic profiling,and phylogenetic analyses show that the biosynthesis of papanridins is prevalent in cacao,grape,blueberry,corn,rice,Arabidopsis,and other species in the plant kingdom.In summary,our study discoveries a group of novel oligomeric flavonoids,namely papanridins,and reveals that a novel FP-mediated polymerization mechanism for the biosynthesis of papanridins in plants.展开更多
Artemisinin-based combination therapy(ACT)forms the first line of malaria treatment.However,the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for ACT.This problem is ma...Artemisinin-based combination therapy(ACT)forms the first line of malaria treatment.However,the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for ACT.This problem is mainly caused by the glandular trichome(GT)-specific biosynthesis of artemisinin in all currently used Artemisia annua cultivars.Here,we report that non-GT cells of self-pollinated inbred A.annua plants can express the artemisinin biosynthetic pathway.Gene expression analysis demonstrated the transcription of six known pathway genes in GT-free leaves and calli of inbred A.annua plants.LC-qTOF-MS/MS analysis showed that these two types of GT-free materials produce artemisinin,artemisinic acid,and arteannuin B.Detailed IR-MALDESI image profiling revealed that these three metabolites and dihydroartemisinin are localized in non-GT cells of leaves of inbred A.annua plants.Moreover,we employed all the above approaches to examine artemisinin biosynthesis in the reported XL annua glandless(gl)mutant.The resulting data demonstrated that leaves of regenerated gl plantlets biosynthesize artemisinin.Codectively,these findings not only add new knowledge leading to a revision of the current dogma of artemisinin biosynthesis inannua but also may expedite innovation of novel metabolic engineering approaches for high and stable production of artemisinin in the future.展开更多
基金funded by the US Department of Agriculture 526614-09725(D.-Y.X.)in 2006.
文摘The discovery of novel flavonoids and elucidation of their biosynthesis are fundamental to understanding their roles in plants and their benefits for human and animal health.Here,we report a new pathway for polymerization of a group of novel oligomeric flavonoids in plants.We engineered red cells for discovering genes of interest involved in the flavonoid pathway and identified a gene encoding a novel flavanol polymerase(FP)localized in the central vacuole.FP catalyzes the polymerization of flavanols,such as epicatechin and catechin,to produce yellowish dimers or oligomers.Structural elucidation shows that these compounds feature a novel oligomeric flaven–flavan(FF)skeleton linked by interflavan–flaven and interflaven bonds,distinguishing them from proanthocyanidins and dehydrodicatechins.Detailed chemical and physical characterizations further confirmed the novel FFs as flavonoids.Mechanistic investigations demonstrated that FP polymerizes flavan-3-ols and flav-2-en-3-ol carbocation,forming dimeric or oligomeric flaven-4→8-flavans,which we term“papanridins.”Data from transgenic experiments,mutant analysis,metabolic profiling,and phylogenetic analyses show that the biosynthesis of papanridins is prevalent in cacao,grape,blueberry,corn,rice,Arabidopsis,and other species in the plant kingdom.In summary,our study discoveries a group of novel oligomeric flavonoids,namely papanridins,and reveals that a novel FP-mediated polymerization mechanism for the biosynthesis of papanridins in plants.
文摘Artemisinin-based combination therapy(ACT)forms the first line of malaria treatment.However,the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for ACT.This problem is mainly caused by the glandular trichome(GT)-specific biosynthesis of artemisinin in all currently used Artemisia annua cultivars.Here,we report that non-GT cells of self-pollinated inbred A.annua plants can express the artemisinin biosynthetic pathway.Gene expression analysis demonstrated the transcription of six known pathway genes in GT-free leaves and calli of inbred A.annua plants.LC-qTOF-MS/MS analysis showed that these two types of GT-free materials produce artemisinin,artemisinic acid,and arteannuin B.Detailed IR-MALDESI image profiling revealed that these three metabolites and dihydroartemisinin are localized in non-GT cells of leaves of inbred A.annua plants.Moreover,we employed all the above approaches to examine artemisinin biosynthesis in the reported XL annua glandless(gl)mutant.The resulting data demonstrated that leaves of regenerated gl plantlets biosynthesize artemisinin.Codectively,these findings not only add new knowledge leading to a revision of the current dogma of artemisinin biosynthesis inannua but also may expedite innovation of novel metabolic engineering approaches for high and stable production of artemisinin in the future.
