{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:19:12Z","timestamp":1787642352112,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Project of Zhejiang Chinese Medical University","award":["2025JKZKTS21"],"award-info":[{"award-number":["2025JKZKTS21"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LZ26H280003"],"award-info":[{"award-number":["LZ26H280003"]}]},{"name":"National Young Qihuang Scholars Training Program, Young Talent Support Project of China Association of Chinese Medicine","award":["CACM-2024-QNRC2-B33"],"award-info":[{"award-number":["CACM-2024-QNRC2-B33"]}]},{"name":"National \u2018Ten-thousand Talents Program\u2019 for Leading Talents of Science and Technology Innovation in China"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474030"],"award-info":[{"award-number":["82474030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3503900"],"award-info":[{"award-number":["2023YFC3503900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Camptotheca acuminata, a tree native to southern China and cultivated for horticultural purposes, has attracted considerable attention due to its ability to synthesize camptothecin-type compounds with potent antitumor activity. Flavonoids and camptothecins share a conserved benzene ring scaffold, suggesting potential crosstalk in their biosynthetic pathways. Metabolic profiling of 1-year-old C. acuminata seedlings revealed tissue-specific accumulation of O-methylated quercetin and camptothecin in the stem phloem. Notably, CaOMT3, one of four clustered O-methyltransferase genes, showed expression levels that positively correlated with rhamnetin accumulation across tissues. Transient transformation in Nicotiana benthamiana, coupled with heterologous expression in vitro, demonstrated that CaOMT1, CaOMT2, and CaOMT3 efficiently methylated 9-hydroxycamptothecin and 10-hydroxycamptothecin. Regarding their flavonoid-methylation abilities, CaOMT1 and CaOMT3 were identified as bifunctional enzymes that targeted the 4\u2032-hydroxyl and 7-hydroxyl groups of quercetin, respectively, whereas CaOMT2 exhibited strict specificity for the 4\u2032-hydroxyl group of quercetin. Unfortunately, CaOMT4 showed no methylation activity toward the tested substrates. The catalytic dyad and key substrate-binding sites of the CaOMTs were identified via molecular docking and subsequently verified by site-directed mutagenesis. F166, M313, and L316 were proposed to be critical for activity toward both quercetin and hydroxycamptothecin. Notably, N261, S309, and T312 were suggested as key amino acids responsible for the lack of 7-O-methylation activity in CaOMT2. Taken together, our findings revealed a bifunctional OMT gene cluster and provided molecular insights into the substrate-binding pockets.<\/jats:p>","DOI":"10.1093\/hr\/uhag145","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:48:51Z","timestamp":1776430131000},"source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <i>O<\/i>\n                    -methyltransferase gene cluster in\n                    <i>Camptotheca acuminata<\/i>\n                    is involved in camptothecins and flavonoids metabolism"],"prefix":"10.1093","volume":"13","author":[{"given":"Qingyan","family":"Ruan","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Hao","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyin","family":"Kai","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Plant Biotechnology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou 310053 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