Nodulisporic acids comprise a group of valuable indole diterpenes that exhibit potent insecticidal activities. We report the identification of a gene cluster in the genome of the filamentous fungus Hypoxylon pulicicidum (Nodulisporium sp.) that contains genes responsible for the biosynthesis of nodulisporic acids. Using Penicillium paxilli as a heterologous host, and through pathway reconstitution experiments, we identified the function of four genes involved in the biosynthesis of the nodulisporic acid core compound, nodulisporic acid F (NAF). Two of these genes (nodM and nodW) are especially significant as they encode enzymes with previously unreported functionality: nodM encodes a 3-geranylgeranylindole epoxidase capable of catalyzing only a single epoxidation step to prime formation of the distinctive ring structure of nodulisporic acids, and nodW encodes the first reported gene product capable of introducing a carboxylic acid moiety to an indole diterpene core structure that acts as a reactive handle for further modification. Here, we present the enzymatic basis for the biosynthetic branch point that gives rise to nodulisporic acids.

中文翻译：

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球孢酸F的异源生物合成

Nodulisporic Acids 包含一组有价值的吲哚二萜，具有强大的杀虫活性。我们报告了丝状真菌 Hypoxylon pulicicidum (Nodulisporium sp.) 基因组中基因簇的鉴定，该基因簇包含负责 nodulisporic 酸生物合成的基因。使用 Paxilli 青霉作为异源宿主，通过通路重建实验，我们确定了四种基因的功能，这些基因参与了球孢酸核心化合物球孢酸 F (NAF) 的生物合成。其中两个基因（nodM 和 nodW）特别重要，因为它们编码的酶具有以前未报告的功能：nodM 编码 3-香叶基香叶基吲哚环氧化酶，该酶仅能催化单个环氧化步骤，以引发球孢酸独特环结构的形成，和 nodW 编码第一个报道的基因产物，能够将羧酸部分引入吲哚二萜核心结构，作为进一步修饰的反应柄。在这里，我们介绍了产生结孢酸的生物合成分支点的酶学基础。