{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:36Z","timestamp":1791400956288,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T00:00:00Z","timestamp":1529539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Plant Journal"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Codeinone reductase (<jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content>) catalyzes the reversible <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\u2010dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (<jats:italic>Papaver somniferum<\/jats:italic>). It also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3\u2010<jats:italic>O<\/jats:italic>\u2010demethylated analogs, <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, the formation of neomorphine by <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> is irreversible. Neopine is a minor substrate for codeine <jats:italic>O<\/jats:italic>\u2010demethylase (<jats:styled-content style=\"fixed-case\">CODM<\/jats:styled-content>), yielding morphine. In the plant, neopine levels are low and neomorphine has not been detected. Silencing of <jats:italic><jats:styled-content style=\"fixed-case\">CODM<\/jats:styled-content><\/jats:italic> leads to accumulation of upstream metabolites, such as codeine and thebaine, but does not result in a shift towards higher relative concentrations of neopine, suggesting a mechanism in the plant for limiting neopine production. In yeast (<jats:italic>Saccharomyces cerevisiae<\/jats:italic>) engineered to produce opiate alkaloids, the catalytic properties of <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> lead to accumulation of neopine and neomorphine as major products. An isoform (<jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content>\u2010B) was isolated from opium poppy chemotype Bea's Choice that showed higher catalytic activity than previously characterized <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content>s, and it yielded mostly neopine <jats:italic>in\u00a0vitro<\/jats:italic> and in engineered yeast. Five catalytically distinct <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> isoforms (<jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content>1.1\u20131.4 and <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content>\u2010B) were used to determine sequence\u2013function relationships that influence product selectivity. Biochemical characterization and site\u2010directed mutagenesis of native <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> isoforms identified four residues (V25, K41, F129 and W279) that affected protein stability, reaction velocity, and product selectivity and output. Improvement of <jats:styled-content style=\"fixed-case\">COR<\/jats:styled-content> performance coupled with an ability to guide pathway flux is necessary to facilitate commercial production of opiate alkaloids in engineered microorganisms.<\/jats:p>","DOI":"10.1111\/tpj.13975","type":"journal-article","created":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T06:19:43Z","timestamp":1526797183000},"page":"631-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy"],"prefix":"10.1111","volume":"95","author":[{"given":"Mehran","family":"Dastmalchi","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth K. S.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Facchini","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Calgary Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1033"},{"key":"e_1_2_8_3_1","first-page":"470","volume-title":"Physiology of Rubber Tree Latex","author":"d'Auzac J.","year":"1989"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502239200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.12.5391"},{"key":"e_1_2_8_6_1","first-page":"1032","article-title":"Novel insights into the organization of laticifer cells: a cell comprising a unified whole system","volume":"172","author":"Castelblanque L.","year":"2016","journal-title":"Plant Physiol."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2015.05.016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-017-9519-z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2683(20001001)21:16<3500::AID-ELPS3500>3.0.CO;2-O"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11103-012-9913-2"},{"key":"e_1_2_8_11_1","article-title":"Comparative protein structure modeling using MODELLER","author":"Eswar N.","year":"2006","journal-title":"Curr. 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