The biaryl scaffold, often showing axial chirality, is a common feature of various fungal natural products. Their biosynthesis requires an oxidative phenol-coupling reaction usually catalyzed by laccases, cytochrome P450 enzymes, or peroxidases. The combination of a laccase and a fasciclin domain-containing (fas) protein is encoded in many biosynthetic gene clusters of biaryls from ascomycetes. However, such phenol-coupling systems including their regio- and stereoselectivity have not been characterized so far. Elucidating the biosynthesis of the antiparasitic binaphthalene sporandol from Chrysosporium merdarium, we demonstrate the combination of a laccase and a fas protein to be crucial for the dimerization reaction. Only the heterologous coproduction of the laccase and the fas protein led to a functional phenol-coupling system, whereas the laccase alone showed no coupling activity. Thus, the laccase/fas protein combination forms an independent group of phenol-coupling enzymes that determines the coupling activity and selectivity of the reaction concurrently and applies to the biosynthesis of many fungal natural products with a biaryl scaffold.

中文翻译：

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Fasciclin蛋白对于漆酶介导的Sporandol生物合成中的选择性苯酚偶联必不可少。

经常表现出轴向手性的联芳基支架是各种真菌天然产物的共同特征。它们的生物合成需要通常由漆酶，细胞色素P450酶或过氧化物酶催化的氧化苯酚偶联反应。漆酶和含有fasciclin域的（fas）蛋白的组合编码在来自子囊菌的联芳基的许多生物合成基因簇中。然而，到目前为止，尚未表征此类苯酚偶联系统，包括其区域选择性和立体选择性。阐明了从金孢孢子菌中合成抗寄生虫双萘二甲酚的生物合成，我们证明了漆酶和fas蛋白的结合对于二聚化反应至关重要。只有漆酶和fas蛋白的异源联产才导致功能性的苯酚偶联系统，而单独的漆酶则没有偶联活性。因此，漆酶/ fas蛋白组合形成了独立的酚偶联酶基团，其同时确定了反应的偶联活性和选择性，并应用于具有联芳基支架的许多真菌天然产物的生物合成。