覆盖范围：截至 2024 年 6 月 苄基异喹啉生物碱 (BIA) 代表了多种源自 L-酪氨酸的植物特有代谢物，具有重要的药理特性，例如抗菌、抗痉挛、抗癌、心血管保护和镇痛作用。有价值的 BIA 的工业生产依赖于从植物中提取；然而，其低浓度和效率的挑战阻碍了药物开发。因此，已经探索了替代方法，包括生物合成和化学酶合成。罂粟和黄连等模式物种在揭示 BIA 的生物合成途径中发挥了关键作用；然而，许多方面，特别是氧化和甲基化等修饰步骤仍不清楚。关键酶，例如 CYP450 和甲基转移酶，在 BIA 主链形成和修饰中发挥着重要作用，这对于了解这些植物特化代谢物的起源和适应性进化至关重要。本综述全面分析了已报道的 BIA 的结构多样性及其在植物谱系中的分布。此外，还总结了 BIA 生物合成的生物合成、进化和催化机制的理解进展。最后，我们讨论了代谢工程的进展和挑战，为 BIA 药物开发和 BIA 生产植物的可持续利用提供了宝贵的见解。

Covering: up to June 2024Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L-tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like Papaver somniferum and Coptis japonica have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, e.g., CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants.