Three cytochrome P450 enzymes catalyse the formation of furanoclerodane precursors in Salvia spp. DOI Open Access
Ruoxi Lin, Haixiu Li, Yiren Xiao

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 17, 2024

Abstract Salvia species native to the Americas are rich in valuable bioactive furanoclerodanes, like psychoactive salvinorin A found divinorum , which is used treatment of opioid addiction. However, there relatively little known about their biosynthesis. To address this, we investigated biosynthesis salviarin, simplest furanoclerodane structure ornamental sage splendens . Using a self-organizing map and mutual rank analysis RNA-seq co-expression data, identified three cytochrome P450 enzymes responsible for converting kolavenol into salviarin precursors, consecutively: annonene, hardwickiic acid hautriwaic acid. As annonene have also been proposed as intermediates A, examine our hypothesis common evolutionary origin pathway between two species, searched homologous genes available data S. The encoded by orthologous from displayed synthase (SdKLS), (SdANS), (SdHDAS) activity respectively, supporting view that these intermediate steps A. We role gene duplication evolution this specific activity. Our work shows how can serve model studying furanoclerodanes contributes understanding specialized metabolism plants, provides new tools produce biotechnological chassis.

Язык: Английский

Theory and scientificity of traditional Chinese medicine DOI Creative Commons
Lanping Guo, Wenjin Zhang, Luqi Huang

и другие.

Science of Traditional Chinese Medicine, Год журнала: 2023, Номер 1(1), С. 26 - 34

Опубликована: Сен. 1, 2023

Abstract The Nobel Prize for artemisinin and the COVID-19 pandemic have heightened interest in disease prevention treatment of traditional Chinese medicine (TCM). However, uncertainty misinformation remain about some key issues. Herein, we discuss current literature showing that, despite TCM gaining recognition, theoretical systems Western rooted different cultural backgrounds huge differences their theories treatments. How to achieve accurate diagnosis TCM, how give scientific treatment, what is mechanism are effect safety all need be more clearly explained require high-quality modern evidence. An emerging consensus exists with help technology methods, it necessary excavate essence that truly conforms laws human life movement development, realize cross-complementation medicine, enhance understanding diseases, enrich promote a new level field sciences.

Язык: Английский

Процитировано

2

Single-cell RNA-seq based elucidation of the antidepressant hyperforin biosynthesisde novoin St. John’s wort DOI Open Access
Song Wu, Ana Luísa Malaco Morotti, Jun Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 29, 2024

Summary Hyperforin is the compound responsible for effectiveness of St. John’s wort ( Hypericum perforatum ) as an antidepressant, but its biosynthesis remains unknown. Gene discovery based on co-expression analysis bulk RNA-sequencing data or genome mining failed to discover missing steps in hyperforin biosynthesis. Here we sequenced tetraploid H. genome. By single-cell RNA-seq, identified a distinct type cells, Hyper wherein de novo takes place. Through pathway reconstitution yeast and tobacco, identify characterize four transmembrane prenyltransferases resolve The polycyclic scaffold created by reaction cascade involving irregular isoprenoid coupling tandem cyclization. Our findings reveal how where biosynthesized that enables synthetic-biology complete pathway. These results deepen our comprehension specialized metabolism at cellular level, anticipate acceleration elucidation plant metabolism.

Язык: Английский

Процитировано

0

CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family DOI Creative Commons
Nicholas Schlecht, Emily R. Lanier, Trine B. Andersen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

SUMMARY The Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset clerodane diterpenoids with broad bioactivities including insect antifeedant properties. Ajugoideae subfamily, in particular, accumulates significant numbers structurally related furanoclerodanes. biosynthetic capacity for formation these retained across most subfamilies, early-diverging Callicarpoideae which forms sister clade to rest Lamiaceae. VacCYP76BK1 , cytochrome P450 monooxygenase from Vitex agnus-castus was previously found catalyze proposed precursor furan and lactone-containing labdane diterpenoids. Through transcriptome-guided pathway exploration, we identified orthologs Ajuga reptans Callicarpa americana. Functional characterization demonstrated that both could oxidative cyclization backbones yield ring. Subsequent investigation revealed total ten CYP76BK1 six subfamilies. analysis available chromosome-scale genomes, four members as syntelogs within conserved syntenic block divergent This suggests an evolutionary lineage predates speciation affirmed conservation function, all catalyzed ring formation. Additionally, some yielded two novel lactone moieties. presence subfamilies closely overlaps distribution reported Together, activities here support their central role furanoclerodane biosynthesis family. Our findings lay groundwork biotechnological applications harness economic potential this promising class compounds. Significance Statement discovery functional diverse chemistry biosynthesis, providing insights into metabolic landscape dynamic evolution plant family over approximately 50 million years. These pave way targeted engineering efforts sustainable production compounds, offering prospects agricultural pharmaceutical applications.

Язык: Английский

Процитировано

0

CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family DOI Creative Commons
Nicholas Schlecht, Emily R. Lanier, Trine B. Andersen

и другие.

The Plant Journal, Год журнала: 2024, Номер 120(3), С. 984 - 997

Опубликована: Сен. 14, 2024

SUMMARY The Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset clerodane diterpenoids with broad bioactivities including insect antifeedant properties. Ajugoideae subfamily, in particular, accumulates significant numbers structurally related furanoclerodanes. biosynthetic capacity for formation these retained across most subfamilies, early‐diverging Callicarpoideae which forms sister clade to rest Lamiaceae. VacCYP76BK1 , cytochrome P450 monooxygenase from Vitex agnus‐castus was previously found catalyze proposed precursor furan and lactone‐containing labdane diterpenoids. Through transcriptome‐guided pathway exploration, we identified orthologs Ajuga reptans Callicarpa americana. Functional characterization demonstrated that both could oxidative cyclization backbones yield ring. Subsequent investigation revealed total 10 CYP76BK1 six subfamilies. analysis available chromosome‐scale genomes, four members as syntelogs within conserved syntenic block divergent This suggests an evolutionary lineage predates speciation affirmed conservation function, all catalyzed ring formation. Additionally, some yielded two novel lactone moieties. presence subfamilies closely overlaps distribution reported Together, activities here support their central role furanoclerodane biosynthesis family. Our findings lay groundwork biotechnological applications harness economic potential this promising class compounds.

Язык: Английский

Процитировано

0

Three cytochrome P450 enzymes catalyse the formation of furanoclerodane precursors in Salvia spp. DOI Open Access
Ruoxi Lin, Haixiu Li, Yiren Xiao

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 17, 2024

Abstract Salvia species native to the Americas are rich in valuable bioactive furanoclerodanes, like psychoactive salvinorin A found divinorum , which is used treatment of opioid addiction. However, there relatively little known about their biosynthesis. To address this, we investigated biosynthesis salviarin, simplest furanoclerodane structure ornamental sage splendens . Using a self-organizing map and mutual rank analysis RNA-seq co-expression data, identified three cytochrome P450 enzymes responsible for converting kolavenol into salviarin precursors, consecutively: annonene, hardwickiic acid hautriwaic acid. As annonene have also been proposed as intermediates A, examine our hypothesis common evolutionary origin pathway between two species, searched homologous genes available data S. The encoded by orthologous from displayed synthase (SdKLS), (SdANS), (SdHDAS) activity respectively, supporting view that these intermediate steps A. We role gene duplication evolution this specific activity. Our work shows how can serve model studying furanoclerodanes contributes understanding specialized metabolism plants, provides new tools produce biotechnological chassis.

Язык: Английский

Процитировано

0