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However, conventional batch processes are limited in their productivity and sustainability. In this study, a stable continuous enzymatic acylation system was developed for the efficient synthesis of flavonoid esters with a particular focus on puerarin palmitate. Key process variables and their interactions were systematically evaluated using statistical approaches, and under optimal conditions, the cumulative conversion and production reached 89.66% and 166.80 mg, respectively. The process was implemented in a continuous stirred-tank reactor (CSTR), maintaining an average conversion of 88.54% over 9 h of operation. The total production and productivity of puerarin palmitate were 1921.21 mg and 51.23 g\/L\/day, respectively, demonstrating the feasibility of continuous production. Ultimately, this study provides a scalable framework for sustainable flavonoid ester synthesis in pharmaceutical and food industries.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06098","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:02:24Z","timestamp":1790791344000},"page":"31748-31756","source":"Crossref","is-referenced-by-count":0,"title":["Statistically Optimized\nContinuous Stirred-Tank Reactor\nfor Efficient and Scalable Enzymatic Synthesis of Puerarin Palmitate"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0492-3763","authenticated-orcid":true,"given":"Eunjeong","family":"Yang","sequence":"first","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0819-3405","authenticated-orcid":true,"given":"Eun Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyerim","family":"Son","sequence":"additional","affiliation":[{"name":"Sangmyung University , , 20 Hongjimun 2-Gil , Jongno-Gu, ,","place":["Seoul, Republic of Korea, 03016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongmok","family":"Yang","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-9422","authenticated-orcid":true,"given":"Taek","family":"Lee","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-2876","authenticated-orcid":true,"given":"Jong-Min","family":"Oh","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Jae","family":"Park","sequence":"additional","affiliation":[{"name":"Ewha Womans University , , ,","place":["Seoul, Republic of Korea, 03760"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hah Young","family":"Yoo","sequence":"additional","affiliation":[{"name":"Sangmyung University , , 20 Hongjimun 2-Gil , Jongno-Gu, ,","place":["Seoul, Republic of Korea, 03016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-7881","authenticated-orcid":true,"given":"Chulhwan","family":"Park","sequence":"additional","affiliation":[{"name":"Kwangwoon University , , 20 Kwangwoon-Ro , Nowon-Gu, ,","place":["Seoul, Republic of Korea, 01897"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"2","key":"2026101408093088700_cit1","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3390\/pr13020350","article-title":"Highly Efficient\nRecovery of Bioactive Puerarin from Roots of Pueraria Lobata Using\nGenerally Recognized as Safe Solvents","volume":"13","author":"Yang","year":"2025","journal-title":"Processes"},{"issue":"17","key":"2026101408093088700_cit2","doi-asserted-by":"publisher","first-page":"5377","DOI":"10.3390\/molecules26175377","article-title":"Plant Flavonoids: Chemical Characteristics\nand Biological Activity","volume":"26","author":"Dias","year":"2021","journal-title":"Molecules"},{"issue":"20","key":"2026101408093088700_cit3","doi-asserted-by":"publisher","first-page":"12605","DOI":"10.3390\/ijms232012605","article-title":"Flavonoids\nas Antidiabetic and Anti-Inflammatory Agents: A Review\non Structural Activity Relationship-Based Studies and Meta-Analysis","volume":"23","author":"Shamsudin","year":"2022","journal-title":"Int. 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