Nguyen Trinh-Don, Dang Thu-Thuy T
Department of Chemistry, Irving K. Barber Faculty of Science, University of British Columbia, Kelowna, BC, Canada.
Front Plant Sci. 2021 Jul 2;12:682181. doi: 10.3389/fpls.2021.682181. eCollection 2021.
Plants produce more than 20,000 nitrogen-containing heterocyclic metabolites called alkaloids. These chemicals serve numerous eco-physiological functions in the plants as well as medicines and psychedelic drugs for human for thousands of years, with the anti-cancer agent vinblastine and the painkiller morphine as the best-known examples. Cytochrome P450 monooxygenases (P450s) play a key role in generating the structural variety that underlies this functional diversity of alkaloids. Most alkaloid molecules are heavily oxygenated thanks to P450 enzymes' activities. Moreover, the formation and re-arrangement of alkaloid scaffolds such as ring formation, expansion, and breakage that contribute to their structural diversity and bioactivity are mainly catalyzed by P450s. The fast-expanding genomics and transcriptomics databases of plants have accelerated the investigation of alkaloid metabolism and many players behind the complexity and uniqueness of alkaloid biosynthetic pathways. Here we discuss recent discoveries of P450s involved in the chemical diversification of alkaloids and how these inform our approaches in understanding plant evolution and producing plant-derived drugs.
植物能产生两万多种含氮杂环代谢产物，即生物碱。数千年来，这些化学物质在植物中发挥着多种生态生理功能，同时也是人类使用的药物和迷幻药，最著名的例子是抗癌药物长春碱和止痛剂吗啡。细胞色素P450单加氧酶（P450s）在产生构成生物碱这种功能多样性基础的结构多样性方面起着关键作用。由于P450酶的活性，大多数生物碱分子都含有大量氧原子。此外，生物碱骨架的形成和重排，如环的形成、扩展和断裂，这些有助于其结构多样性和生物活性的过程主要由P450s催化。植物基因组学和转录组学数据库的快速扩展加速了对生物碱代谢的研究，以及对生物碱生物合成途径的复杂性和独特性背后众多因素的研究。在此，我们讨论了近期关于参与生物碱化学多样化的P450s的发现，以及这些发现如何为我们理解植物进化和生产植物源药物的方法提供信息
