{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:47:34Z","timestamp":1790084854143,"version":"4.0.1"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"17","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82225043"],"award-info":[{"award-number":["82225043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0900600"],"award-info":[{"award-number":["2018YFA0900600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Acdmemy of Sciences","award":["XDB27020205"],"award-info":[{"award-number":["XDB27020205"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,4,25]]},"abstract":"<jats:p>\n                    The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial biosynthetic enzymes of TAs and especially the characteristic tropane skeletons, we generated the chromosome-level genome assemblies of cocaine-producing\n                    <jats:italic>Erythroxylum novogranatense<\/jats:italic>\n                    (Erythroxylaceae, rosids clade) and hyoscyamine-producing\n                    <jats:italic>Anisodus acutangulus<\/jats:italic>\n                    (Solanaceae, asterids clade). Comparative genomic and phylogenetic analysis suggested that the lack of spermidine synthase\/\n                    <jats:italic>N<\/jats:italic>\n                    -methyltransferase (\n                    <jats:italic>En<\/jats:italic>\n                    SPMT1) in ancestral asterids species contributed to the divergence of polyamine (spermidine or putrescine) methylation in cocaine and hyoscyamine biosynthesis. Molecular docking analysis and key site mutation experiments suggested that ecgonone synthases CYP81AN15 and CYP82M3 adopt different active-site architectures to biosynthesize the same product ecgonone from the same substrate in Erythroxylaceae and Solanaceae. Further synteny analysis showed different evolutionary origins and trajectories of CYP81AN15 and CYP82M3, particularly the emergence of\n                    <jats:italic>CYP81AN15<\/jats:italic>\n                    through the neofunctionalization of ancient tandem duplication genes. The combination of structural biology and comparative genomic analysis revealed that ecgonone methyltransferase, which is responsible for the biosynthesis of characteristic 2-substituted carboxymethyl group in cocaine, evolved from the tandem copies of salicylic acid methyltransferase by the mutations of critical E216 and S153 residues. Overall, we provided strong evidence for the independent origins of serial TA biosynthetic enzymes on the genomic and structural level, underlying the chemotypic convergence of TAs in phylogenetically distant species.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2302448120","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T15:11:55Z","timestamp":1681744315000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":27,"title":["Genomic and structural basis for evolution of tropane alkaloid biosynthesis"],"prefix":"10.1073","volume":"120","author":[{"given":"Yong-Jiang","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tain","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-3938","authenticated-orcid":false,"given":"John\u00a0C.","family":"D\u2019Auria","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Leibniz Institute for Plant Genetics and Crop Plant Research Ortsteil Gatersleben, Seeland D-06466, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-8556","authenticated-orcid":false,"given":"Sheng-Xiong","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-85498-4_1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9422(99)00475-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11286-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","unstructured":"B. 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