Plant natural products have served as a prominent source of medicines throughout human history and are still used today as clinically approved pharmaceuticals. However, many medicinal plants that produce useful compounds are slow growing or recalcitrant to cultivation, making it difficult to investigate the underlying genetic/enzymatic machinery responsible for biosynthesis. To better understand the metabolism of bioactive natural products in slow‐growing medicinal plants, we used D₂O labeling and LC–MS‐based metabolomics to explore the biosynthesis of medically relevant alkaloids in three plant species. Our results provide evidence for sites of active biosynthesis for these alkaloids and demonstrate that D₂O labeling can be used as a general method to determine sites of active secondary metabolism over relatively short‐timescales. We anticipate that these results will facilitate discovery of complete metabolic pathways for plant natural products of medicinal importance, especially for approaches that rely upon transcriptomics and knowledge of active metabolism to identify biosynthetic enzymes. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4319–4330, 2018

中文翻译：

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D2O 标记用于测量药用植物中天然产物的活性生物合成


植物天然产物在整个人类历史中一直是重要的药物来源，并且至今仍被用作临床批准的药物。然而，许多产生有用化合物的药用植物生长缓慢或难以栽培，使得研究负责生物合成的潜在遗传/酶机制变得困难。为了更好地了解生长缓慢的药用植物中生物活性天然产物的代谢，我们使用 D ₂ O 标记和基于 LC-MS 的代谢组学来探索三种植物中医学相关生物碱的生物合成。我们的结果为这些生物碱的活性生物合成位点提供了证据，并证明 D ₂ O 标记可用作在相对较短的时间内确定活性次生代谢位点的通用方法。我们预计这些结果将有助于发现具有药用价值的植物天然产物的完整代谢途径，特别是依赖转录组学和活性代谢知识来识别生物合成酶的方法。 © 2018 美国化学工程师学会AIChE J ，64：4319–4330，2018