Terpenoids constitute a structurally diverse group of natural products with wide applications in the pharmaceutical, nutritional, flavor and fragrance industries. Fungi are known to produce a large variety of terpenoids, yet fungal terpene synthases remain largely unexploited. Here, we report the sesquiterpene network and gene clusters of the black poplar mushroom Agrocybe aegerita. Among 11 putative sesquiterpene synthases (STSs) identified in its genome, nine are functional, including two novel synthases producing viridiflorol and viridiflorene. On this basis, an additional 1133 STS homologues from higher fungi have been curated and used for a sequence similarity network to probe isofunctional STS groups. With the focus on two STS groups, one producing viridiflorene/viridiflorol and one Δ6-protoilludene, the isofunctionality was probed and verified. Three new Δ6-protoilludene synthases and two new viridflorene/viridiflorol synthases from five different fungi were correctly predicted. The study herein serves as a fundamental predictive framework for the discovery of fungal STSs and biosynthesis of novel terpenoids. Furthermore, it becomes clear that fungal STS function differs between the phyla Ascomycota and Basidiomycota with the latter phylum being more dominant in the overall number and variability. This study aims to encourage the scientific community to further work on fungal STS and the products, biological functions, and potential applications of this vast source of natural products.

中文翻译：

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茶树菇作为鉴定高等真菌中倍半萜烯生物合成酶的途径。

萜类化合物构成一组结构多样的天然产物，广泛应用于制药，营养，调味和香料行业。已知真菌会产生各种各样的萜类化合物，但真菌萜烯合酶仍未开发。在这里，我们报道了黑杨蘑菇Agrocybe aegerita的倍半萜烯网络和基因簇。在其基因组中鉴定出的11种假定的倍半萜烯合酶（STS）中，有9种具有功能，其中包括两种新的产生viridiflorol和viridiflorene的合酶。在此基础上，已整理了来自高级真菌的其他1133个STS同源物，并将其用于序列相似性网络以探测同功能的STS基团。着眼于两个STS组，一个生产维地弗洛林/维地弗洛尔，一个生产Δ6-protoilludene，同功能性被探测和验证。正确预测了来自5种不同真菌的3种新的Δ6-proudilludene合酶和2种新的viridflorene / viridiflorol合酶。本文的研究作为发现真菌STS和生物合成新型萜类化合物的基本预测框架。此外，很明显真菌子囊菌和梭状芽孢杆菌之间的真菌STS功能有所不同，后者在总体数量和变异性上更为占优势。这项研究旨在鼓励科学界进一步研究真菌STS及其产品，生物学功能以及这种大量天然产物的潜在应用。本文的研究为真菌STS的发现和新型萜类化合物的生物合成提供了基本的预测框架。此外，很明显真菌子囊菌和梭状芽孢杆菌之间的真菌STS功能有所不同，后者在总体数量和变异性上更为占优势。这项研究旨在鼓励科学界进一步研究真菌STS及其产品，生物学功能以及这种天然来源的潜在应用。本文的研究作为发现真菌STS和生物合成新型萜类化合物的基本预测框架。此外，很明显真菌子囊菌和梭状芽孢杆菌之间的真菌STS功能有所不同，后者在总体数量和变异性上更为占优势。这项研究旨在鼓励科学界进一步研究真菌STS及其产品，生物学功能以及这种大量天然产物的潜在应用。