Terpendole E is the first natural product inhibitor of kinesin Eg5. Because terpendole E production is unstable, we isolated and analyzed the terpendole E biosynthetic gene cluster, which consists of seven genes encoding three P450 monooxygenases (TerP, TerQ, and TerK), an FAD-dependent monooxygenase (TerM), a terpene cyclase (TerB), and two prenyltransferases (TerC and TerF). Gene knockout and feeding experiments revealed that terpendole E is a key intermediate in terpendole biosynthesis and is produced by the action of the key enzyme TerQ from paspaline, a common biosynthetic intermediate of indole-diterpenes. TerP converts terpendole E to a downstream intermediate specific to terpendole biosynthesis and converts paspaline to shunt metabolites. We successfully overproduced terpendole E by disrupting theterPgene. We propose that terpendole E is a key biosynthetic intermediate of terpendoles and related indole-diterpenes.

中文翻译：

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Terpendole E，一种驱动蛋白Eg5抑制剂，是生产真菌Chaunopycnis alba的吲哚-二萜的关键生物合成中间体。

萜烯E是驱动蛋白Eg5的第一种天然产物抑制剂。由于萜烯E生产不稳定，我们分离并分析了萜烯E生物合成基因簇，该簇由编码三个P450单加氧酶（TerP，TerQ和TerK），FAD依赖单加氧酶（TerM），萜烯环化酶（TerB）的七个基因组成）和两个异戊二烯基转移酶（TerC和TerF）。基因敲除和饲养实验表明，萜烯E是萜烯生物合成中的关键中间体，是由Paspaline（吲哚-二萜的常见生物合成中间体）的关键酶TerQ产生的。TerP将萜烯E转化为对萜烯生物合成具有特异性的下游中间体，并将Paspaline转化为分流代谢物。我们通过破坏terP基因成功地生产了萜烯E。