{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:58:07Z","timestamp":1788188287089,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T00:00:00Z","timestamp":1344470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Plant Journal"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Papaverine, a major benzylisoquinoline alkaloid in opium poppy (<jats:italic>Papaver somniferum<\/jats:italic>), is used as a vasodilator and antispasmodic. Conversion of the initial intermediate (<jats:italic>S<\/jats:italic>)\u2010norcoclaurine to papaverine involves 3\u2032\u2010hydroxylation, four <jats:italic>O\u2010<\/jats:italic>methylations and dehydrogenation. However, our understanding of papaverine biosynthesis remains controversial more than a century after an initial scheme was proposed. <jats:italic>In vitro<\/jats:italic> assays and <jats:italic>in vivo<\/jats:italic> labeling studies have been insufficient to establish the sequence of conversions, the potential role of the intermediate (<jats:italic>S<\/jats:italic>)\u2010reticuline, and the enzymes involved. We used virus\u2010induced gene silencing in opium poppy to individually suppress the expression of six genes with putative roles in papaverine biosynthesis. Suppression of the gene encoding coclaurine <jats:italic>N<\/jats:italic>\u2010methyltransferase dramatically increased papaverine levels at the expense of <jats:italic>N<\/jats:italic>\u2010methylated alkaloids, indicating that the main biosynthetic route to papaverine proceeds via <jats:italic>N\u2010<\/jats:italic>desmethylated compounds rather than through (<jats:italic>S<\/jats:italic>)\u2010reticuline. Suppression of genes encoding (<jats:italic>S<\/jats:italic>)\u20103\u2032\u2010hydroxy\u2010<jats:italic>N\u2010<\/jats:italic>methylcoclaurine 4\u2010<jats:italic>O\u2010<\/jats:italic>methyltransferase and norreticuline 7\u2010<jats:italic>O\u2010<\/jats:italic>methyltransferase, which accept certain <jats:italic>N\u2010<\/jats:italic>desmethylated alkaloids, reduced papaverine content. In contrast, suppression of genes encoding <jats:italic>N\u2010<\/jats:italic>methylcoclaurine 3\u2032\u2010hydroxylase or reticuline 7\u2010<jats:italic>O\u2010<\/jats:italic>methyltransferase, which are specific for <jats:italic>N\u2010<\/jats:italic>methylated alkaloids, did not affect papaverine levels. Suppression of norcoclaurine 6\u2010<jats:italic>O\u2010<\/jats:italic>methyltransferase transcript levels significantly suppressed total alkaloid accumulation, implicating (<jats:italic>S<\/jats:italic>)\u2010coclaurine as a key branch\u2010point intermediate. The differential detection of <jats:italic>N\u2010<\/jats:italic>desmethylated compounds in response to suppression of specific genes highlights the primary route to papaverine.<\/jats:p>","DOI":"10.1111\/j.1365-313x.2012.05084.x","type":"journal-article","created":{"date-parts":[[2012,6,22]],"date-time":"2012-06-22T22:39:53Z","timestamp":1340404793000},"page":"331-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy"],"prefix":"10.1111","volume":"72","author":[{"given":"Isabel","family":"Desgagn\u00e9\u2010Penix","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Facchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767070-00003"},{"key":"e_1_2_6_3_1","first-page":"189","article-title":"Tilden Lecture: the biosynthesis of alkaloids","author":"Battersby A.R.","year":"1963","journal-title":"Proc. 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