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Here, we present an interesting example of how tandem duplicated UDP\u2010glycosyltransferases undergo neofunctionalization and shape the chemical diversity of triterpenoid saponins in the Cucurbitaceae family. A chromosome\u2010level genome of\n                    <jats:italic>Siraitia grosvenorii<\/jats:italic>\n                    was assembled and aligned with multiple cucurbit genomes, revealing a specific UGT73AM tandem duplication responsible for regio\u2010selective glycosylation (e.g. the rare 1,4\u2010linked disaccharide) of diverse saponins such as mogrosides, ginsenosides, and momordicines. Comparative genomics depicted the evolutionary trajectory of a universal saponin\u2010biosynthesizing UGT73 tandem arrays syntenously preserved across core eudicots, where lineage\u2010specific UGT copies contribute to distinct metabolic phenotypes. A crystal structure of SgUGT73AM30 (mogrol 25\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010glycosyltransferase) in complex with UDP and mogrol was obtained to elucidate the molecular basis of the regio\u2010specific decoration on vicinal diol of the substrates. Altogether, these findings provide insights into tandem duplication\u2010driven diversification of glycosyltransferases and lay the foundation for engineered glycosylation of valuable triterpenoid saponins.\n                  <\/jats:p>","DOI":"10.1002\/advs.76159","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:14:17Z","timestamp":1781810057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tandem Duplication\u2010Driven Neofunctionalization of UDP\u2010Glycosyltransferases Shapes the Diversification of Triterpenoid Saponins in the Cucurbitaceae"],"prefix":"10.1002","volume":"13","author":[{"given":"Guangyi","family":"Wang","sequence":"first","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Li","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Dai","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"},{"name":"State Key Laboratory of Bioreactor Engineering School of Biotechnology East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Wu","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotao","family":"Yan","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenfei","family":"Tian","sequence":"additional","affiliation":[{"name":"CAS\u2010Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant Sciences Institute of Plant Physiology and Ecology Chinese Academy of Sciences  Shanghai China"},{"name":"Technology Center Shanghai Tobacco Group Co., Ltd.  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