中国科学院分子植物科学卓越创新中心李大鹏小组研究出尼古丁的完全生物合成。相关论文于2026年4月1日发表在《细胞》杂志上。

课题组人员发现，最终的偶联反应是通过尿苷二磷酸(UDP)-糖基转移酶的糖基化来稳定的，通过A622还原和激活，通过分子间类似曼尼奇的立体选择性反应浓缩，随后被小檗碱桥酶样（BBL）氧化，最后被β-葡萄糖苷酶去糖基化生成尼古丁。一个5组分代谢物聚集在液泡膜上，引导尼古丁的生物合成和运输。课题组研究人员在体外和体内异种重组了这种代谢物。废除这些成分中的任何一种都会消耗尼古丁的积累。一种多药毒性化合物外源离子（MATE）转运体是控制异花酮植物尼古丁产生的关键物质，从而提高植物抗虫能力。这项工作完成了尼古丁的生物合成途径，并为分子间曼尼奇样反应提供了重要的见解，曼尼奇反应是许多植物生物碱支架形成的基本机制。

据了解，尼古丁是烟草中令人上瘾的强效杀虫生物碱，它塑造了人类历史、农业和生产它的植物。然而，涉及尼古丁生物合成的酶的步骤和反应机制仍然是未知的。

附：英文原文

Title: Complete biosynthesis of nicotine

Author: Lijing Chang, Zhen Xu, Purong Deng, Ning Zhang, Tingrui He, Xinying Liu, Wenqi He, Anqi Zheng, Wenjun Hu, Mingjun Pan, Wenjuan Li, Rayko Halitschke, Ran Li, Minrui Fan, Ian T. Baldwin, Yu Zhang, Dapeng Li

Issue&Volume: 2026-04-01

Abstract: Nicotine, tobacco’s addictive and potent insecticidal alkaloid, has shaped human history, agriculture, and the plants that produce it. However, the enzymatic steps and reaction mechanisms involved in nicotine biosynthesis remain elusive. Here, we reveal that the final coupling reaction is stabilized by glycosylation via a uridine diphosphate (UDP)-glycosyltransferase, reduced and activated by an A622, condensed through a stereoselective intermolecular Mannich-like reaction, sequentially oxidized by a berberine bridge enzyme-like (BBL), and finally deglycosylated by a β-glucosidase to yield nicotine. A 5-component metabolon assembles at vacuolar membranes to channel both nicotine biosynthesis and its transport. We reconstituted this metabolon both in vitro and heterologously in vivo. Abrogating any of these components depletes nicotine accumulations. A multidrug and toxic compound extrusion (MATE) transporter is essential for efficiently engineering nicotine production in heterologous plant species, which confers pest resistance. This work completes the nicotine biosynthesis pathway and provides critical insights into the intermolecular Mannich-like reaction, a fundamental mechanism for scaffold formation in many plant alkaloids.

DOI: 10.1016/j.cell.2026.03.034

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00335-1