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This review provides a systematic and multidimensional overview of nicotine research, including its biosynthesis, regulatory network, ecological functions, and application potential. In contrast to approaches primarily focused on nicotine reduction or elimination, we propose an integrated framework that connects core metabolic pathways, ecosystem-level interactions, and synthetic biology developments. By systematically surveying the literature, we highlight several key unresolved issues (including the incomplete understanding of transport pathways) and discuss potential avenues for achieving a paradigm shift. The objective is to transition nicotine research from a predominantly harm-reduction-focused paradigm to one that proactively designs novel functionalities and develops high-value, practical applications.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06034","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:01:17Z","timestamp":1789758077000},"page":"29700-29714","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms and\nApplication Prospects of Nicotine from\nPlant Defense to the Frontiers of Bioengineering"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-0186","authenticated-orcid":true,"given":"Chaonan","family":"Shi","sequence":"first","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Xue","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofu","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Li","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifan","family":"He","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozong","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhengzhou University of Light Industry , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of CNTC , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiliang","family":"Tang","sequence":"additional","affiliation":[{"name":"Michigan Technological University , , , ,","place":["Houghton, Michigan, United States, 49931"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of CNTC , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"issue":"1","key":"2026093009080166000_cit1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00346-w","article-title":"Tobacco and Nicotine Use","volume":"8","author":"Foll","year":"2022","journal-title":"Nat.\nRev. 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