{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:45:55Z","timestamp":1793015155968,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T00:00:00Z","timestamp":1470700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/page\/authors\/licenses"}],"funder":[{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["ERC-2012-ADG_20120314"],"award-info":[{"award-number":["ERC-2012-ADG_20120314"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","award":["n.a."],"award-info":[{"award-number":["n.a."]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001825","name":"Ministry of Science, Innovation and Higher Education | Danish Agency for Science, Technology and Innovation","doi-asserted-by":"publisher","award":["12-131834"],"award-info":[{"award-number":["12-131834"]}],"id":[{"id":"10.13039\/501100001825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001825","name":"Ministry of Science, Innovation and Higher Education | Danish Agency for Science, Technology and Innovation","doi-asserted-by":"publisher","award":["12-131834"],"award-info":[{"award-number":["12-131834"]}],"id":[{"id":"10.13039\/501100001825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006233","name":"DOE | National Renewable Energy Laboratory, Office of Energy Efficiency and Renewable Energy","doi-asserted-by":"publisher","award":["DE-FC02-07ER64494"],"award-info":[{"award-number":["DE-FC02-07ER64494"]}],"id":[{"id":"10.13039\/100006233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,8,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Ingenol mebutate is a diterpene ester with a highly complex macrocyclic structure that has been approved for the treatment of actinic keratosis, a precondition of skin cancer. The current production of ingenol mebutate through plant extraction or chemical synthesis is inefficient and costly. Here, we describe the discovery of a biosynthetic route in\n                    <jats:italic>Euphorbia lathyris<\/jats:italic>\n                    L. (caper spurge) in which regio-specific oxidation of casbene is followed by an unconventional cyclization to yield jolkinol C, a probable key intermediate in the biosynthesis of macrocyclic diterpenes, including ingenol mebutate. These results can facilitate the biotechnological production of this high-value pharmaceutical and discovery of new biosynthetic intermediates with important bioactivities.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1607504113","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T22:53:38Z","timestamp":1470783218000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":95,"title":["Oxidation and cyclization of casbene in the biosynthesis of\n                    <i>Euphorbia<\/i>\n                    factors from mature seeds of\n                    <i>Euphorbia lathyris<\/i>\n                    L."],"prefix":"10.1073","volume":"113","author":[{"given":"Dan","family":"Luo","sequence":"first","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Callari","sequence":"additional","affiliation":[{"name":"Evolva AS, CH-4153 Reinach, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Hamberger","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sileshi Gizachew","family":"Wubshet","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten T.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Andersen-Ranberg","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"},{"name":"Center for Synthetic Biology \u201cbioSYNergy,\u201d DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn M.","family":"Hallstr\u00f6m","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, School of Biotechnology, Kungliga Tekniska H\u00f6gskolan Royal Institute of Technology, SE-171 21 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-3119","authenticated-orcid":false,"given":"Harald","family":"Heider","sequence":"additional","affiliation":[{"name":"Evolva AS, CH-4153 Reinach, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birger","family":"Lindberg M\u00f8ller","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"},{"name":"Center for Synthetic Biology \u201cbioSYNergy,\u201d DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-1807","authenticated-orcid":false,"given":"Dan","family":"Staerk","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Hamberger","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;"},{"name":"Center for Synthetic Biology \u201cbioSYNergy,\u201d DK-1871 Frederiksberg C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,8,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1021\/cr078350s","article-title":"Chemical and pharmacological research of the plants in genus Euphorbia","volume":"108","author":"Shi QW","year":"2008","unstructured":"QW Shi, XH Su, H Kiyota, Chemical and pharmacological research of the plants in genus Euphorbia. Chem Rev 108, 4295\u20134327 (2008).","journal-title":"Chem Rev"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/np0203537","article-title":"A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris)","volume":"66","author":"Appendino G","year":"2003","unstructured":"G Appendino, , A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris). J Nat Prod 66, 140\u2013142 (2003).","journal-title":"J Nat Prod"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1021\/jm030787e","article-title":"Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead","volume":"46","author":"Corea G","year":"2003","unstructured":"G Corea, , Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead. J Med Chem 46, 3395\u20133402 (2003).","journal-title":"J Med Chem"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1021\/np800295m","article-title":"Variability in content of the anti-AIDS drug candidate prostratin in Samoan populations of Homalanthus nutans","volume":"71","author":"Johnson HE","year":"2008","unstructured":"HE Johnson, SA Banack, PA Cox, Variability in content of the anti-AIDS drug candidate prostratin in Samoan populations of Homalanthus nutans. J Nat Prod 71, 2041\u20132044 (2008).","journal-title":"J Nat Prod"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1158\/0008-5472.CAN-03-3403","article-title":"Characterization of the interaction of ingenol 3-angelate with protein kinase C","volume":"64","author":"Kedei N","year":"2004","unstructured":"N Kedei, , Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64, 3243\u20133255 (2004).","journal-title":"Cancer Res"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1440-0960.2008.00497.x","article-title":"PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: Results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study","volume":"50","author":"Siller G","year":"2009","unstructured":"G Siller, K Gebauer, P Welburn, J Katsamas, SM Ogbourne, PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: Results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J Dermatol 50, 16\u201322 (2009).","journal-title":"Australas J Dermatol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1055\/s-2000-8568","article-title":"Diterpenoids from Euphorbia peplus","volume":"66","author":"Hohmann J","year":"2000","unstructured":"J Hohmann, F Evanics, L Berta, T Bart\u00f3k, Diterpenoids from Euphorbia peplus. Planta Med 66, 291\u2013294 (2000).","journal-title":"Planta Med"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1126\/science.1241606","article-title":"14-step synthesis of (+)-ingenol from (+)-3-carene","volume":"341","author":"J\u00f8rgensen L","year":"2013","unstructured":"L J\u00f8rgensen, , 14-step synthesis of (+)-ingenol from (+)-3-carene. Science 341, 878\u2013882 (2013).","journal-title":"Science"},{"key":"e_1_3_4_9_2","first-page":"2338","article-title":"Cocarcinogenic principles from the seed oil of Croton tiglium and from other Euphorbiaceae","volume":"28","author":"Hecker E","year":"1968","unstructured":"E Hecker, Cocarcinogenic principles from the seed oil of Croton tiglium and from other Euphorbiaceae. Cancer Res 28, 2338\u20132349 (1968).","journal-title":"Cancer Res"},{"key":"e_1_3_4_10_2","first-page":"325","article-title":"On the active principles of the spurge family. III. Skin irritant and cocarcinogenic factors from the caper spurge","volume":"84","author":"Adolf W","year":"1975","unstructured":"W Adolf, E Hecker, On the active principles of the spurge family. III. Skin irritant and cocarcinogenic factors from the caper spurge. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 84, 325\u2013344 (1975).","journal-title":"Z Krebsforsch Klin Onkol Cancer Res Clin Oncol"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1055\/s-0032-1317415","article-title":"Semisynthesis of ingenol 3-angelate (PEP005): Efficient stereoconservative angeloylation of alcohols","volume":"23","author":"Liang X","year":"2012","unstructured":"X Liang, G Grue-S\u00f8rensen, AK Petersen, T H\u00f6gberg, Semisynthesis of ingenol 3-angelate (PEP005): Efficient stereoconservative angeloylation of alcohols. Synlett 23, 2647\u20132652 (2012).","journal-title":"Synlett"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nrmicro3240","article-title":"Semi-synthetic artemisinin: A model for the use of synthetic biology in pharmaceutical development","volume":"12","author":"Paddon CJ","year":"2014","unstructured":"CJ Paddon, JD Keasling, Semi-synthetic artemisinin: A model for the use of synthetic biology in pharmaceutical development. Nat Rev Microbiol 12, 355\u2013367 (2014).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1039\/9781849737845-00330","article-title":"Disruptive innovation: Channeling photosynthetic electron flow into light-driven synthesis of high-value products","volume":"1","author":"M\u00f8ller BL","year":"2014","unstructured":"BL M\u00f8ller, Disruptive innovation: Channeling photosynthetic electron flow into light-driven synthesis of high-value products. Syn Biol 1, 330\u2013339 (2014).","journal-title":"Syn Biol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.phytochem.2010.06.001","article-title":"Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae","volume":"71","author":"Kirby J","year":"2010","unstructured":"J Kirby, , Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae. Phytochemistry 71, 1466\u20131473 (2010).","journal-title":"Phytochemistry"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1104\/pp.62.4.598","article-title":"Biosynthesis of the diterpene phytoalexin casbene: Partial purification and characterization of casbene synthetase from Ricinis communis","volume":"62","author":"Dueber MT","year":"1978","unstructured":"MT Dueber, W Adolf, CA West, Biosynthesis of the diterpene phytoalexin casbene: Partial purification and characterization of casbene synthetase from Ricinis communis. Plant Physiol 62, 598\u2013603 (1978).","journal-title":"Plant Physiol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1104\/pp.113.218347","article-title":"Gene discovery of modular diterpene metabolism in nonmodel systems","volume":"162","author":"Zerbe P","year":"2013","unstructured":"P Zerbe, , Gene discovery of modular diterpene metabolism in nonmodel systems. Plant Physiol 162, 1073\u20131091 (2013).","journal-title":"Plant Physiol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1104\/pp.010768","article-title":"Transgenic production of epoxy fatty acids by expression of a cytochrome P450 enzyme from Euphorbia lagascae seed","volume":"128","author":"Cahoon EB","year":"2002","unstructured":"EB Cahoon, KG Ripp, SE Hall, B McGonigle, Transgenic production of epoxy fatty acids by expression of a cytochrome P450 enzyme from Euphorbia lagascae seed. Plant Physiol 128, 615\u2013624 (2002).","journal-title":"Plant Physiol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1105\/tpc.114.129668","article-title":"Production of bioactive diterpenoids in the Euphorbiaceae depends on evolutionarily conserved gene clusters","volume":"26","author":"King AJ","year":"2014","unstructured":"AJ King, GD Brown, AD Gilday, TR Larson, IA Graham, Production of bioactive diterpenoids in the Euphorbiaceae depends on evolutionarily conserved gene clusters. Plant Cell 26, 3286\u20133298 (2014).","journal-title":"Plant Cell"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1111\/j.1742-4658.2011.08211.x","article-title":"A short-chain dehydrogenase involved in terpene metabolism from Zingiber zerumbet","volume":"278","author":"Okamoto S","year":"2011","unstructured":"S Okamoto, , A short-chain dehydrogenase involved in terpene metabolism from Zingiber zerumbet. FEBS J 278, 2892\u20132900 (2011).","journal-title":"FEBS J"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1271\/bbb.66.566","article-title":"Biosynthesis of rice phytoalexin: Enzymatic conversion of 3beta-hydroxy-9beta-pimara-7,15-dien-19,6beta-olide to momilactone A","volume":"66","author":"Atawong A","year":"2002","unstructured":"A Atawong, M Hasegawa, O Kodama, Biosynthesis of rice phytoalexin: Enzymatic conversion of 3beta-hydroxy-9beta-pimara-7,15-dien-19,6beta-olide to momilactone A. Biosci Biotechnol Biochem 66, 566\u2013570 (2002).","journal-title":"Biosci Biotechnol Biochem"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1104\/pp.104.053298","article-title":"Monoterpene metabolism. Cloning, expression, and characterization of (-)-isopiperitenol\/(-)-carveol dehydrogenase of peppermint and spearmint","volume":"137","author":"Ringer KL","year":"2005","unstructured":"KL Ringer, EM Davis, R Croteau, Monoterpene metabolism. Cloning, expression, and characterization of (-)-isopiperitenol\/(-)-carveol dehydrogenase of peppermint and spearmint. Plant Physiol 137, 863\u2013872 (2005).","journal-title":"Plant Physiol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.abb.2012.09.013","article-title":"Molecular cloning and functional characterization of borneol dehydrogenase from the glandular trichomes of Lavandula x intermedia","volume":"528","author":"Sarker LS","year":"2012","unstructured":"LS Sarker, M Galata, ZA Demissie, SS Mahmoud, Molecular cloning and functional characterization of borneol dehydrogenase from the glandular trichomes of Lavandula x intermedia. Arch Biochem Biophys 528, 163\u2013170 (2012).","journal-title":"Arch Biochem Biophys"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1002\/anie.201510650","article-title":"Expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis","volume":"55","author":"Andersen-Ranberg J","year":"2016","unstructured":"J Andersen-Ranberg, , Expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis. Angew Chem Int Ed Engl 55, 2142\u20132146 (2016).","journal-title":"Angew Chem Int Ed Engl"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1021\/np5009416","article-title":"Dual high-resolution \u03b1-glucosidase and radical scavenging profiling combined with HPLC-HRMS-SPE-NMR for identification of minor and major constituents directly from the crude extract of Pueraria lobata","volume":"78","author":"Liu B","year":"2015","unstructured":"B Liu, , Dual high-resolution \u03b1-glucosidase and radical scavenging profiling combined with HPLC-HRMS-SPE-NMR for identification of minor and major constituents directly from the crude extract of Pueraria lobata. J Nat Prod 78, 294\u2013300 (2015).","journal-title":"J Nat Prod"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1016\/S0040-4039(00)93940-6","article-title":"The structure of new lathyrane diterpenes, jolkinols a, b, c, and d, from Euphorbia jolkini Boiss","volume":"17","author":"Uemura D","year":"1976","unstructured":"D Uemura, K Nobuhara, Y Nakayama, Y Shizuri, Y Hirata, The structure of new lathyrane diterpenes, jolkinols a, b, c, and d, from Euphorbia jolkini Boiss. Tetrahedron Lett 17, 4593\u20134596 (1976).","journal-title":"Tetrahedron Lett"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"E81","DOI":"10.1073\/pnas.1419547112","article-title":"Investigation of terpene diversification across multiple sequenced plant genomes","volume":"112","author":"Boutanaev AM","year":"2015","unstructured":"AM Boutanaev, , Investigation of terpene diversification across multiple sequenced plant genomes. Proc Natl Acad Sci USA 112, E81\u2013E88 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/B978-0-12-404634-4.00013-9","article-title":"De novo synthesis of high-value plant sesquiterpenoids in yeast","volume":"517","author":"Nguyen TD","year":"2012","unstructured":"TD Nguyen, G MacNevin, DK Ro, De novo synthesis of high-value plant sesquiterpenoids in yeast. Methods Enzymol 517, 261\u2013278 (2012).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/tpj.13162","article-title":"Heartwood-specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)-santalol fragrance biosynthesis","volume":"86","author":"Celedon JM","year":"2016","unstructured":"JM Celedon, , Heartwood-specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)-santalol fragrance biosynthesis. Plant J 86, 289\u2013299 (2016).","journal-title":"Plant J"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1002\/hlca.200900105","article-title":"Three terpenoids and a tocopherol\u2010related compound from Ricinus communis","volume":"92","author":"Tan QG","year":"2009","unstructured":"QG Tan, XH Cai, ZZ Du, XD Luo, Three terpenoids and a tocopherol\u2010related compound from Ricinus communis. Helv Chim Acta 92, 2762\u20132768 (2009).","journal-title":"Helv Chim Acta"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1021\/sb300128r","article-title":"Redirecting photosynthetic reducing power toward bioactive natural product synthesis","volume":"2","author":"Nielsen AZ","year":"2013","unstructured":"AZ Nielsen, , Redirecting photosynthetic reducing power toward bioactive natural product synthesis. ACS Synth Biol 2, 308\u2013315 (2013).","journal-title":"ACS Synth Biol"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/sb400136f","article-title":"Redirecting photosynthetic electron flow into light-driven synthesis of alternative products including high-value bioactive natural compounds","volume":"3","author":"Lassen LM","year":"2014","unstructured":"LM Lassen, , Redirecting photosynthetic electron flow into light-driven synthesis of alternative products including high-value bioactive natural compounds. ACS Synth Biol 3, 1\u201312 (2014).","journal-title":"ACS Synth Biol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1104\/pp.111.185843","article-title":"Evolution of diterpene metabolism: Sitka spruce CYP720B4 catalyzes multiple oxidations in resin acid biosynthesis of conifer defense against insects","volume":"157","author":"Hamberger B","year":"2011","unstructured":"B Hamberger, T Ohnishi, B Hamberger, A S\u00e9guin, J Bohlmann, Evolution of diterpene metabolism: Sitka spruce CYP720B4 catalyzes multiple oxidations in resin acid biosynthesis of conifer defense against insects. Plant Physiol 157, 1677\u20131695 (2011).","journal-title":"Plant Physiol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/nprot.2013.084","article-title":"De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis","volume":"8","author":"Haas BJ","year":"2013","unstructured":"BJ Haas, , De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis. Nat Protoc 8, 1494\u20131512 (2013).","journal-title":"Nat Protoc"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/j.1467-7652.2009.00434.x","article-title":"pEAQ: Versatile expression vectors for easy and quick transient expression of heterologous proteins in plants","volume":"7","author":"Sainsbury F","year":"2009","unstructured":"F Sainsbury, EC Thuenemann, GP Lomonossoff, pEAQ: Versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol J 7, 682\u2013693 (2009).","journal-title":"Plant Biotechnol J"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-60761-723-5_13","article-title":"USER cloning and USER fusion: The ideal cloning techniques for small and big laboratories","volume":"643","author":"Nour-Eldin HH","year":"2010","unstructured":"HH Nour-Eldin, F Geu-Flores, BA Halkier, USER cloning and USER fusion: The ideal cloning techniques for small and big laboratories. Methods Mol Biol 643, 185\u2013200 (2010).","journal-title":"Methods Mol Biol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"e122","DOI":"10.1093\/nar\/gkl635","article-title":"Advancing uracil-excision based cloning towards an ideal technique for cloning PCR fragments","volume":"34","author":"Nour-Eldin HH","year":"2006","unstructured":"HH Nour-Eldin, BG Hansen, MH N\u00f8rholm, JK Jensen, BA Halkier, Advancing uracil-excision based cloning towards an ideal technique for cloning PCR fragments. Nucleic Acids Res 34, e122 (2006).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_37_2","first-page":"245","volume-title":"Methods in Molecular Biology","author":"Bach SS","year":"2014","unstructured":"SS Bach, , Plant Isoprenoids Methods and Protocols. Methods in Molecular Biology, ed MR Concepci\u00f3n (Springer, New York) Vol 1153, 245\u2013255 (2014)."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0076-6879(96)72008-6","article-title":"Yeast expression of animal and plant P450s in optimized redox environments","volume":"272","author":"Pompon D","year":"1996","unstructured":"D Pompon, B Louerat, A Bronine, P Urban, Yeast expression of animal and plant P450s in optimized redox environments. Methods Enzymol 272, 51\u201364 (1996).","journal-title":"Methods Enzymol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1607504113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1607504113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T10:39:59Z","timestamp":1654598399000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1607504113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,9]]},"references-count":38,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2016,8,23]]}},"alternative-id":["10.1073\/pnas.1607504113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1607504113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,9]]},"assertion":[{"value":"2016-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}