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Abstract：
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.
摘要：
联芳基支架，通常显示轴向手性，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催化的氧化酚偶联反应，细胞色素P450酶，或过氧化物酶。漆酶和含fasciclin结构域（fas）蛋白的组合在子囊菌的许多生物合成基因簇中编码。然而,这样的苯酚偶联体系,包括它们的区域选择性和立体选择性至今还没有被表征。阐明了金孢子菌的抗寄生虫联萘孢子醇的生物合成，我们证明了漆酶和fas蛋白的组合对于二聚化反应至关重要。只有漆酶和fas蛋白的异源共同生产导致了功能性的酚偶联系统，而单独的漆酶没有显示偶联活性。因此，漆酶/fas蛋白组合形成一组独立的酚偶联酶，其同时决定反应的偶联活性和选择性，并适用于具有联芳基支架的许多真菌天然产物的生物合成。
