Muro-Villanueva Fabiola, Nett Ryan S
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Phytochem Rev. 2023 Dec 12. doi: 10.1007/s11101-023-09901-z.
The alkaloids are a major class of nitrogen-containing plant specialized metabolites that function as both toxic defense compounds and useful pharmaceuticals. Understanding the biosynthesis of these molecules offers a glimpse into the impressive diversity of metabolic chemistry found within plants and also enables the metabolic engineering of valuable alkaloids in other biological systems. Within the last decade, there have been major advances in our knowledge of alkaloid metabolism within multiple plant lineages, and this has allowed for the complete, or near complete elucidation of several alkaloid biosynthetic pathways. This work has been instrumental for establishing the chemical logic by which alkaloids are synthesized in plants and has also highlighted enzymatic functions that were not previously recognized or identified within plant metabolism. In this review, we highlight notable examples of unexpected or otherwise noteworthy enzyme-catalyzed reactions that have recently been identified within alkaloid biosynthesis. Our goal is to emphasize two major areas: 1) non-canonical reactions catalyzed by enzyme families with otherwise well-known roles in alkaloid biosynthesis, and 2) enzyme families that have emerged as having a broader role in alkaloid metabolism than previously appreciated. Beyond compiling these examples, we also discuss mechanistic details of novel enzyme classes that may be useful for future identification and study of non-canonical enzyme activity in alkaloid biosynthesis. Collectively, the recent discovery of several previously unidentified enzyme activities in alkaloid biosynthesis indicates that there is still much to uncover about plant specialized metabolism. Thus, the continued study of alkaloid biosynthesis will not only provide us with the underlying enzymes necessary to engineer production of valuable molecules with medicinal potential, but will also yield foundational insight on the chemistry that is possible in the plant kingdom.
生物碱是一类主要的含氮植物特殊代谢产物，既作为有毒防御化合物，又作为有用的药物发挥作用。了解这些分子的生物合成，能让我们一窥植物中代谢化学令人惊叹的多样性，还能实现其他生物系统中有价值生物碱的代谢工程改造。在过去十年里，我们对多个植物谱系中生物碱代谢的认识取得了重大进展，这使得几条生物碱生物合成途径得以完整或近乎完整地阐明。这项工作有助于确立植物中生物碱合成的化学逻辑，还突出了植物代谢中以前未被认识或鉴定的酶功能。在这篇综述中，我们重点介绍了最近在生物碱生物合成中发现的意外或其他值得注意的酶催化反应的显著例子。我们的目标是强调两个主要方面：1）在生物碱生物合成中具有其他众所周知作用的酶家族催化的非经典反应，以及2）在生物碱代谢中发挥比以前认识到的更广泛作用的酶家族。除了汇编这些例子，我们还讨论了新型酶类的机制细节，这些细节可能有助于未来鉴定和研究生物碱生物合成中的非经典酶活性。总的来说，最近在生物碱生物合成中发现了几种以前未鉴定的酶活性，这表明植物特殊代谢仍有许多有待揭示的地方。因此，对生物碱生物合成的持续研究不仅将为我们提供工程化生产具有药用潜力的有价值分子所需的基础酶，还将为植物王国中可能的化学过程提供基本见解。
