{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:16:30Z","timestamp":1773465390371,"version":"3.50.1"},"reference-count":33,"publisher":"Proceedings of the National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,2]]},"abstract":"<jats:p>\n                    Madagascar periwinkle (\n                    <jats:italic>Catharanthus roseus<\/jats:italic>\n                    ) 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\n                    <jats:italic>C. roseus<\/jats:italic>\n                    cDNA encoding an\n                    <jats:italic>S<\/jats:italic>\n                    -adenosyl-L-methionine-dependent\n                    <jats:italic>N<\/jats:italic>\n                    methyltransferase that catalyzes a nitrogen methylation involved in vindoline biosynthesis. Recombinant enzyme produced in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    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                    <jats:italic>N<\/jats:italic>\n                    methyltransferase is most similar at the amino acid level to the plastidic \u03b3-tocopherol\n                    <jats:italic>C<\/jats:italic>\n                    methyltransferases of vitamin E biosynthesis, suggesting an evolutionary link between these two functionally disparate methyltransferases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1009003107","type":"journal-article","created":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T00:19:23Z","timestamp":1287447563000},"page":"18793-18798","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":93,"title":["Homolog of tocopherol\n                    <i>C<\/i>\n                    methyltransferases catalyzes\n                    <i>N<\/i>\n                    methylation in anticancer alkaloid biosynthesis"],"prefix":"10.1073","volume":"107","author":[{"given":"David K.","family":"Liscombe","sequence":"first","affiliation":[{"name":"Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139"}]},{"given":"Aimee R.","family":"Usera","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139"}]},{"given":"Sarah E.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139"}]}],"member":"341","published-online":{"date-parts":[[2010,10,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1039\/b512615k","article-title":"Chemistry and biology of monoterpene indole alkaloid biosynthesis","volume":"23","author":"O\u2019Connor SE","year":"2006","unstructured":"SE O\u2019Connor, JJ Maresh, Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat Prod Rep 23, 532\u2013547 (2006).","journal-title":"Nat Prod Rep"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2174\/0929867043455846","article-title":"The Catharanthus alkaloids: Pharmacognosy and biotechnology","volume":"11","author":"van Der Heijden R","year":"2004","unstructured":"R van Der Heijden, DI Jacobs, W Snoeijer, D Hallard, R Verpoorte, The Catharanthus alkaloids: Pharmacognosy and biotechnology. Curr Med Chem 11, 607\u2013628 (2004).","journal-title":"Curr Med Chem"},{"key":"e_1_3_4_3_2","first-page":"123","volume-title":"Anticancer Agents from Natural Products","author":"Gu\u00e9ritte F","year":"2005","unstructured":"F Gu\u00e9ritte, J Fahy, The Vinca Alkaloids. Anticancer Agents from Natural Products, eds GML Cragg, D Kingston, DJ Newman (Taylor & Francis, Boca Raton, FL), pp. 123\u2013136 (2005)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"11966","DOI":"10.1073\/pnas.0401323101","article-title":"Stereocontrolled total synthesis of (+)-vincristine","volume":"101","author":"Kuboyama T","year":"2004","unstructured":"T Kuboyama, S Yokoshima, H Tokuyama, T Fukuyama, Stereocontrolled total synthesis of (+)-vincristine. Proc Natl Acad Sci USA 101, 11966\u201311970 (2004).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1021\/ja0177049","article-title":"Stereocontrolled total synthesis of (+)-vinblastine","volume":"124","author":"Yokoshima S","year":"2002","unstructured":"S Yokoshima, et al., Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 124, 2137\u20132139 (2002).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1023\/A:1005894001516","article-title":"Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent-dioxygenase involved in the biosynthesis of vindoline in Catharanthus roseus (L.) G. Don","volume":"34","author":"Vazquez-Flota F","year":"1997","unstructured":"F Vazquez-Flota, E De Carolis, AM Alarco, V De Luca, Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent-dioxygenase involved in the biosynthesis of vindoline in Catharanthus roseus (L.) G. Don. 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Plant J 53, 225\u2013236 (2008).","journal-title":"Plant J"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1046\/j.1365-313x.1998.00174.x","article-title":"The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer","volume":"14","author":"St-Pierre B","year":"1998","unstructured":"B St-Pierre, P Laflamme, AM Alarco, V De Luca, The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer. 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