{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:36:56Z","timestamp":1768725416666,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Science and Technology Major Project","award":["TM202302H005"],"award-info":[{"award-number":["TM202302H005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82425058"],"award-info":[{"award-number":["82425058"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82373935"],"award-info":[{"award-number":["82373935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glycosylation serves as an effective strategy to enhance the solubility, bioavailability, and pharmacological activity of polyhydroxyphenols. In this study, we explored the glycosylation of natural and natural-inspired phenolic compounds using the glycosyltransferase AbCGT and evaluated the anti-renal fibrotic potential of the resulting glycosides. Among them, 1,3,5,8-tetrahydroxyxanthone 5-O-\u03b2-D-glucopyranoside (2-1a), synthesized via the regioselective 5-O-glycosylation of demethylbellidifolin, demonstrated significant anti-renal fibrotic activity. In contrast, its homologous glycosyltransferase, UGT73AE1, predominantly glycosylated demethylbellidifolin at the 3-OH position. Molecular docking studies revealed the structural basis for this regioselectivity difference. To enhance the production of 2-1a, we established a UDP-glucose (UDPG) recycling system by coupling AbCGT with Glycine max sucrose synthase (GmSuSy) and subsequently optimized the reaction conditions. Furthermore, targeted mutagenesis of AbCGT informed by molecular docking analysis identified a F138A mutant that enhanced glycosylation yield by 2.3-fold. This work develops a novel glycosyltransferase-based catalytic system and identifies a new compound with potential anti-renal fibrotic activity.<\/jats:p>","DOI":"10.3390\/molecules31020309","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:21:13Z","timestamp":1768494073000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regioselective Glycosylation of Demethylbellidifolin by Glycosyltransferase AbCGT Yields Potent Anti-Renal Fibrosis Compound"],"prefix":"10.3390","volume":"31","author":[{"given":"Limin","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-1270","authenticated-orcid":false,"given":"Shichao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"Ji","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guozhang","family":"Long","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulan","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-9539","authenticated-orcid":false,"given":"Gang","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingya","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Key Laboratory of Glyco-Drug Research of Zhejiang Province, School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhong","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Key Laboratory of Glyco-Drug Research of Zhejiang Province, School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nrd.2016.67","article-title":"The next generation of therapeutics for chronic kidney disease","volume":"15","author":"Breyer","year":"2016","journal-title":"Nat. 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