A homolog of tocopherol C-methyltransferases catalyzes N-methylation in anticancer alkaloid biosynthesis
Name
Liscombe-2010-Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis.pdf
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1.15 MB
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Author(s)
Liscombe, David K.
Usera, Aimee R.
O'Connor, Sarah Ellen
Date Issued
November 2010
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Liscombe, David K., Aimee R. Usera, and Sarah E. O’Connor. “Homolog of Tocopherol C Methyltransferases Catalyzes N Methylation in Anticancer Alkaloid Biosynthesis.” Proceedings of the National Academy of Sciences 107.44 (2010) : 18793 -18798. Copyright ©2010 by the National Academy of Sciences
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Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1009003107
