10/24/2022 0 Comments Cytoscape transcription factor![]() WRKY proteins were initially classified into three groups based on the number of WRKY domains and the type of zinc finger. Also, atypical WRKY motifs have been suggested, containing the consensus sequence W(R/K)(K/R)Y. Several variants of the WRKYGQK motif have been reported, including WRKYGEK and WRKYGKK. The name WRKY refers to a highly conserved domain with nearly 60 amino acids that contains the signature WRKYGQK sequence and a non-typical zinc-finger-like motif (C 2H 2 or C 2HC). The three dashed arrows indicate that the camptothecin biosynthetic pathway in camptothecin-producing plants is still unknown.Īs a large family of transcription factors (TFs), the WRKYs have been reported to participate in various plant developmental and physiological processes and responses. The putative camptothecin biosynthetic pathway in O. Still, the transcriptional regulation of camptothecin biosynthesis remains largely unknown in the camptothecin-producing plant O. acuminata, in which strictosidinic acid serves as the final precursor. Interestingly, the biosynthesis of strictosidine in O. Finally, strictosidine is converted to camptothecin through various biochemical reactions such as oxidation, reduction, cyclization, and isomerization. Strictosidine synthase (OpSTR) then catalyzes the formation of strictosidine from tryptamine and secologanin. The iridoid pathway includes nine consecutive enzymatic steps initiated by geranyl diphosphate synthase (GPPS) and ending with the reduction of loganin to secologanin catalyzed by secologanin synthase (OpSLS). In the shikimate pathway, tryptophan decarboxylase (OpTDC) catalyzes tryptamine production from tryptophan. pumila is synthesized from the important precursor strictosidine supplied by tryptamine in the shikimate pathway and secologain in the iridoid pathway ( Fig. Similar to other MIAs, camptothecin in O. pumila has the advantages of a short growth cycle, high camptothecin content, and easy genetic transformation, which render it an ideal model plant for the study of camptothecin biosynthesis and regulation. ![]() Compared with woody camptothecin-producing plants, O. As a naturally occurring plant monoterpene indole alkaloid (MIA), camptothecin accumulates in various distantly related plants, including Camptotheca acuminata (Nyssaceae), Nothapodytes nimmoniana (Icacinaceae), and Ophiorrhiza pumila (Rubiaceae). Camptothecin exhibits remarkable antitumor activity by inhibiting topoisomerase I enzyme, and its two derivatives (topotecan and irinotecan) are widely used as anti-cancer chemotherapeutic drugs. Treatment options for cancer include surgery, anti-cancer medicines, and radiation therapy, administered alone or in combination. Our data provide direct evidence for the involvement of WRKYs in the regulation of camptothecin biosynthesis and offer valuable information for enriching the production of camptothecin in plant systems.Īs the leading cause of death globally, cancer can cause nearly 10 million deaths in a year, posing a severe threat to human health. Further biochemical assays showed that OpWRKY6 negatively regulates camptothecin biosynthesis from both the iridoid and shikimate pathways by directly downregulating the gene expression of OpGES, Op10HGO, Op7DLH, and OpTDC. Conversely, camptothecin accumulation increased in OpWRKY6 knockout lines. Overexpression of OpWRKY6 significantly reduced the accumulation of camptothecin compared with the control. Based on spatial expression and co-expression, we targeted the candidate gene OpWRKY6. Phylogenetic and multiple sequence alignment analyses divided the OpWRKY proteins into three subfamilies. ![]() We identified 46 OpWRKY genes unevenly distributed on the 11 chromosomes of O. However, little is currently known about their involvement in camptothecin biosynthesis in O. ![]() The DNA-binding WRKY transcription factors have a key regulatory role in secondary metabolite biosynthesis in plants. Ophiorrhiza pumila is an ideal plant model for the study of camptothecin production, with various advantages for studying camptothecin biosynthesis and regulation. Camptothecin is a chemotherapeutic drug widely used to treat various cancers. ![]()
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