Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Department of Biochemistry and Metabolism, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Science. 2023 Jan 27;379(6630):361-368. doi: 10.1126/science.adf1017. Epub 2023 Jan 26.
Triterpenes with complex scaffold modifications are widespread in the plant kingdom. Limonoids are an exemplary family that are responsible for the bitter taste in citrus (e.g., limonin) and the active constituents of neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite the commercial value of limonoids, a complete biosynthetic route has not been described. We report the discovery of 22 enzymes, including a pair of neofunctionalized sterol isomerases, that catalyze 12 distinct reactions in the total biosynthesis of kihadalactone A and azadirone, products that bear the signature limonoid furan. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations.
三萜类化合物具有复杂的支架修饰，广泛存在于植物界中。柠檬苦素是一个典型的家族，它负责柑橘类水果的苦味（如柠碱）和印楝油的有效成分，印楝油是一种广泛使用的生物杀虫剂（如印楝素）。尽管柠檬苦素具有商业价值，但尚未描述其完整的生物合成途径。我们报告了发现 22 种酶，包括一对新功能化的甾醇异构酶，它们在 kihadalactone A 和 azadirone 的总生物合成中催化 12 个不同的反应，这两种产物都具有标志性的柠檬苦素呋喃。这些结果使获得有价值的柠檬苦素成为可能，并为发现和重建需要多次骨架重排和氧化的植物三萜类生物合成途径提供了模板。
