{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:34:08Z","timestamp":1791214448381,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:00:00Z","timestamp":1172707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolic Engineering"],"published-print":{"date-parts":[[2007,3]]},"DOI":"10.1016\/j.ymben.2006.10.004","type":"journal-article","created":{"date-parts":[[2006,11,7]],"date-time":"2006-11-07T08:33:12Z","timestamp":1162888392000},"page":"169-176","source":"Crossref","is-referenced-by-count":84,"title":["Metabolic engineering with a morphine biosynthetic P450 in opium poppy surpasses breeding"],"prefix":"10.1016","volume":"9","author":[{"given":"Susanne","family":"Frick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kramell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni M.","family":"Kutchan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymben.2006.10.004_bib1","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1038\/nbt1033","article-title":"RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy","volume":"22","author":"Allen","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymben.2006.10.004_bib2","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1105\/tpc.015396","article-title":"A tale of three cell types: alkaloid biosynthesis is localized to sieve elements in opium poppy","volume":"15","author":"Bird","year":"2003","journal-title":"Plant Cell"},{"key":"10.1016\/j.ymben.2006.10.004_bib3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-2007-969727","article-title":"A second pathway for the terminal steps in the biosynthesis of morphine","volume":"50","author":"Brochmann-Hanssen","year":"1984","journal-title":"Planta Med."},{"key":"10.1016\/j.ymben.2006.10.004_bib4","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1073\/pnas.90.12.5391","article-title":"A brief history of opiates, opioid peptides, and opioid receptors","volume":"90","author":"Brownstein","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2006.10.004_bib5","doi-asserted-by":"crossref","first-page":"12929","DOI":"10.1073\/pnas.96.22.12929","article-title":"Interactions among enzymes of the Arabidopsis flavonoid biosynthetic pathway","volume":"96","author":"Burbulis","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"4","key":"10.1016\/j.ymben.2006.10.004_bib6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1089\/dna.1983.2.329","article-title":"A method for isolation of intact translationally active ribonucleic acid","volume":"2","author":"Cathala","year":"1983","journal-title":"DNA"},{"key":"10.1016\/j.ymben.2006.10.004_bib7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1023\/B:PLAN.0000009268.45851.95","article-title":"Antisense-mediated down-regulation of putrescine N-methyltransferase activity in transgenic Nicotiana tabacum L. can lead to elevated levels of anatabine at the expense of nicotine","volume":"53","author":"Chintapakorn","year":"2003","journal-title":"Plant Mol. Biol."},{"issue":"10","key":"10.1016\/j.ymben.2006.10.004_bib8","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1071\/FP03126","article-title":"Genetic transformation in commercial Tasmanian cultivars of opium poppy, Papaver somniferum, and movement of transgenic pollen in the field","volume":"30","author":"Chitty","year":"2003","journal-title":"Funct. Plant Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib9","doi-asserted-by":"crossref","first-page":"9969","DOI":"10.1073\/pnas.88.22.9969","article-title":"Molecular cloning, expression and induction of berberine bridge enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack","volume":"88","author":"Dittrich","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2006.10.004_bib10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1360-1385(99)01471-5","article-title":"Flavonoids and isoflavonoids\u2014a gold mine for metabolic engineering","volume":"4","author":"Dixon","year":"1999","journal-title":"Trends Plant Sci."},{"key":"10.1016\/j.ymben.2006.10.004_bib11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.arplant.52.1.29","article-title":"Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications","volume":"52","author":"Facchini","year":"2001","journal-title":"Annu. Rev. Plant Physiol. Plant Mol. Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib12","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1104\/pp.112.4.1669","article-title":"Molecular cloning and characterization of berberine bridge enzyme genes from opium poppy","volume":"112","author":"Facchini","year":"1996","journal-title":"Plant Physiol."},{"key":"10.1016\/j.ymben.2006.10.004_bib13","doi-asserted-by":"crossref","unstructured":"Facchini, P.J., Bird, D.A., MacLeod, B.P., Park, S.-U., Samanani, N., 2003. Multiple levels of control in the regulation of alkaloid biosynthesis. In: Romeo, J.T. (Ed.), Integrative Phytochemistry: From Ethnobotany to Molecular Ecology, vol. 37. In: Romeo, J.T. (Ed.), Recent Advances in Phytochemistry, Pergamon, Amsterdam, pp. 143\u2013180.","DOI":"10.1016\/S0079-9920(03)80022-9"},{"issue":"6","key":"10.1016\/j.ymben.2006.10.004_bib14","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s11248-004-2892-6","article-title":"Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme 1 (anti-bbe 1) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots","volume":"13","author":"Frick","year":"2004","journal-title":"Trans. Res."},{"key":"10.1016\/j.ymben.2006.10.004_bib15","doi-asserted-by":"crossref","unstructured":"Frick, S., Kramell, R., Larkin, P.J., Kutchan, T.M., 2005a. Studying morphine biosynthesis using transgenic opium poppy (Papaver somniferum L.). In: Palaniswamy, U.R., Craker, L.E., Gardner, Z.E. (Eds.), Proc. WOCMAP III, vol. 6: Traditional Medicine & Nutraceuticals, Acta Hort. 680, 37\u201343.","DOI":"10.17660\/ActaHortic.2005.680.4"},{"issue":"5","key":"10.1016\/j.ymben.2006.10.004_bib16","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1021\/np0496643","article-title":"Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivars","volume":"68","author":"Frick","year":"2005","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ymben.2006.10.004_bib17","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0031-9422(99)00600-7","article-title":"Distribution of morphinan and benzo[c]phenanthridine alkaloid gene transcript accumulation in Papaver somniferum","volume":"53","author":"Huang","year":"2000","journal-title":"Phytochemistry"},{"key":"10.1016\/j.ymben.2006.10.004_bib18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1006\/mben.2001.0205","article-title":"Metabolic engineering of plants for alkaloid production","volume":"4","author":"Hughes","year":"2002","journal-title":"Metabol. Eng."},{"key":"10.1016\/j.ymben.2006.10.004_bib19","series-title":"The Opium Poppy. A Monograph","author":"Husain","year":"1983"},{"key":"10.1016\/j.ymben.2006.10.004_bib20","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1104\/pp.105.065904","article-title":"Cassava plants with a depleted cyanogenic glucoside content in leaves and tubers. Distribution of cyanogenic glucosides, their site of synthesis and transport, and blockage of the biosynthesis by RNA interference technology","volume":"139","author":"J\u00f8rgensen","year":"2005","journal-title":"Plant Physiol"},{"key":"10.1016\/j.ymben.2006.10.004_bib21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.pbi.2005.03.014","article-title":"Metabolon formation and metabolic channelling in the biosynthesis of plant natural products","volume":"8","author":"J\u00f8rgensen","year":"2005","journal-title":"Curr. Opin. Plant Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib22","first-page":"253","article-title":"Molecular genetics of plant alkaloid biosynthesis","volume":"vol. 50","author":"Kutchan","year":"1998"},{"key":"10.1016\/j.ymben.2006.10.004_bib23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.pbi.2005.03.009","article-title":"A role for intra- and intercellular translocation in natural product biosynthesis","volume":"8","author":"Kutchan","year":"2005","journal-title":"Curr. Opin. Plant Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib24","unstructured":"Kutchan, T.M., Frick, S., Weid, M., Engineering plant alkaloid biosynthetic pathways\u2014Progress and prospects. In: Nes, W.D., Lewis, N.G. (Eds.), Advances in Plant Biochemistry and Molecular Biology, vol. 1. In: Bohnert, H.J., Nguyen, H.T. (Eds.), Bioengineering and Molecular Biology of Plant Pathways. Elsevier Science Ltd., Oxford, in press."},{"key":"10.1016\/j.ymben.2006.10.004_bib25","unstructured":"Larkin, P.J., Chitty, J.A., Brettell, R.I.S., 1999. Methods for plant transformation and regeneration. International patent publication number WO 99\/34663."},{"key":"10.1016\/j.ymben.2006.10.004_bib26","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nbt1091-963","article-title":"A DNA transformation-competent Arabidopsis genomic library in Agrobacterium","volume":"9","author":"Lazo","year":"1991","journal-title":"Bio\/Technol."},{"key":"10.1016\/j.ymben.2006.10.004_bib27","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1093\/pcp\/pch126","article-title":"Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene","volume":"45","author":"Lee","year":"2004","journal-title":"Plant Cell Physiol."},{"key":"10.1016\/j.ymben.2006.10.004_bib28","doi-asserted-by":"crossref","first-page":"8915","DOI":"10.1073\/pnas.141237298","article-title":"Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomease and methanofuran synthase","volume":"98","author":"Mahmoud","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2006.10.004_bib29","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.phytochem.2004.01.005","article-title":"Cosuppression of limonene-3-hydroxylase in peppermint promotes accumulation of limonene in the essential oil","volume":"65","author":"Mahmoud","year":"2004","journal-title":"Phytochemistry"},{"key":"10.1016\/j.ymben.2006.10.004_bib30","unstructured":"Maniatis, T., Fritsch, E.F., Sambrook, J. (Eds.), 1982. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York."},{"key":"10.1016\/j.ymben.2006.10.004_bib31","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/423823a","article-title":"Producing decaffeinated coffee plants","volume":"423","author":"Ogita","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.ymben.2006.10.004_bib32","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s11103-004-0393-x","article-title":"Application of RNAi to confirm theobromine as the major intermediate for caffeine biosynthesis in coffee plants with potential for construction of decaffeinated varieties","volume":"54","author":"Ogita","year":"2004","journal-title":"Plant Mol. Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib33","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1105\/tpc.004077","article-title":"A polyamine metabolon involving aminopropyl transferase complexes in Arabidopsis","volume":"14","author":"Panicot","year":"2002","journal-title":"Plant Cell"},{"key":"10.1016\/j.ymben.2006.10.004_bib34","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1104\/pp.010741","article-title":"Antisense RNA-mediated suppression of benzophenanthridine alkaloid biosynthesis in transgenic cell cultures of California poppy","volume":"128","author":"Park","year":"2002","journal-title":"Plant Physiol."},{"key":"10.1016\/j.ymben.2006.10.004_bib35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1023\/A:1021199311049","article-title":"Modulation of berberine bridge enzyme levels in transgenic root cultures of California poppy alters the accumulation of benzophenanthridine alkaloids","volume":"51","author":"Park","year":"2003","journal-title":"Plant Mol. Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib36","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1046\/j.1365-313X.1998.00085.x","article-title":"Molecular cloning and functional heterologous expression of two alleles encoding (S)-N-methylcoclaurine 3\u2032-hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450 dependent monooxygenase of benzylisoquinoline alkaloid biosynthesis","volume":"13","author":"Pauli","year":"1998","journal-title":"Plant J."},{"key":"10.1016\/j.ymben.2006.10.004_bib37","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/jxb\/eri067","article-title":"Overexpression of tropinone reductase alters alkaloid composition in Atropa belladonna root cultures","volume":"56","author":"Richter","year":"2005","journal-title":"J. Exp. Bot."},{"key":"10.1016\/j.ymben.2006.10.004_bib38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1006\/abbi.1997.0374","article-title":"Cloning and heterologous expression of cytochrome P450 reductases from the Papaveraceae","volume":"348","author":"Rosco","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ymben.2006.10.004_bib39","unstructured":"United Nations, 2004. United Nations Publication INCB Narcotic Drugs\u2014Technical Reports Estimated World Requirements for 2005\u2014Statistics for 2003, United Nations, New York."},{"issue":"5","key":"10.1016\/j.ymben.2006.10.004_bib40","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1046\/j.1365-313X.1999.00470.x","article-title":"Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum","volume":"18","author":"Unterlinner","year":"1999","journal-title":"Plant J."},{"key":"10.1016\/j.ymben.2006.10.004_bib41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1023\/A:1008966404981","article-title":"Engineering the plant cell factory for secondary metabolite production","volume":"9","author":"Verpoorte","year":"2000","journal-title":"Trans. Res."},{"key":"10.1016\/j.ymben.2006.10.004_bib42","doi-asserted-by":"crossref","first-page":"13957","DOI":"10.1073\/pnas.0405704101","article-title":"The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum","volume":"101","author":"Weid","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2006.10.004_bib43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev.arplant.55.031903.141714","article-title":"Metabolic channeling in plants","volume":"55","author":"Winkel","year":"2004","journal-title":"Annu. Rev. Plant Biol."},{"key":"10.1016\/j.ymben.2006.10.004_bib44","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1073\/pnas.95.4.1601","article-title":"Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells","volume":"95","author":"Ye","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2006.10.004_bib45","doi-asserted-by":"crossref","first-page":"6786","DOI":"10.1073\/pnas.0401391101","article-title":"Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures","volume":"101","author":"Zhang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Metabolic Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717606001078?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717606001078?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T03:27:13Z","timestamp":1555903633000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096717606001078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["S1096717606001078"],"URL":"https:\/\/doi.org\/10.1016\/j.ymben.2006.10.004","relation":{},"ISSN":["1096-7176"],"issn-type":[{"value":"1096-7176","type":"print"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}