Mechanisms and Application Prospects of Nicotine from Plant Defense to the Frontiers of Bioengineering.

Despite significant progress in understanding the regulatory mechanisms of nicotine synthesis and in reduction strategies, the complex roles of nicotine in metabolism, stress responses, and bioactive potential remain underexplored. 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.