GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:20956330
Citation |
Liscombe, DK, Usera, AR and O'Connor, SE (2010) Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 107:18793-8 |
---|---|
Abstract |
Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drugs vinblastine and vincristine, bisindole alkaloids derived from the dimerization of the terpenoid indole alkaloids vindoline and catharanthine. Full elucidation of the biosynthetic pathways of these compounds is a prerequisite for metabolic engineering efforts that will improve production of these costly molecules. However, despite the medical and commercial importance of these natural products, the biosynthetic pathways remain poorly understood. Here we report the identification and characterization of a C. roseus cDNA encoding an S-adenosyl-L-methionine-dependent N methyltransferase that catalyzes a nitrogen methylation involved in vindoline biosynthesis. Recombinant enzyme produced in Escherichia coli is highly substrate specific, displaying a strict requirement for a 2,3-dihydro bond in the aspidosperma skeleton. The corresponding gene transcript is induced in methyl jasmonate-elicited seedlings, along with the other known vindoline biosynthetic transcripts. Intriguingly, this unique N methyltransferase is most similar at the amino acid level to the plastidic γ-tocopherol C methyltransferases of vitamin E biosynthesis, suggesting an evolutionary link between these two functionally disparate methyltransferases. |
Links |
PubMed PMC2973921 Online version:10.1073/pnas.1009003107 |
Keywords |
Alkaloids/biosynthesis; Alkaloids/chemistry; Antineoplastic Agents, Phytogenic/biosynthesis; Antineoplastic Agents, Phytogenic/chemistry; Base Sequence; Catharanthus/enzymology; Catharanthus/genetics; Escherichia coli/genetics; Methylation; Methyltransferases/chemistry; Methyltransferases/genetics; Methyltransferases/metabolism; Molecular Sequence Data; Plant Proteins/biosynthesis; Plant Proteins/chemistry; Plant Proteins/genetics; Recombinant Proteins/biosynthesis; Recombinant Proteins/chemistry; Substrate Specificity |
edit table |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0008170: N-methyltransferase activity |
ECO:0000314: |
F |
Figure 3 and the paragraph explaining the results of the essay explain how the protein has N-methyltransferase activity. |
complete | ||||
enables |
GO:0008170: N-methyltransferase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
See Help:References for how to manage references in GONUTS.