PDF(Pubmed)
Abstract：
Labdane-related diterpenoids (LRDs) in fungi are a pharmaceutically important, but underexplored family of natural products. In the biosynthesis of fungal LRDs, bifunctional terpene cyclases (TCs) consisting of αβγ domains are generally used to synthesize the polycyclic skeletones of LRDs. Herein, we conducted genome mining of LRDs in our fungal genome database and identified a unique pair of TCs, AsPS and AsCPS, in the fungus Arthrinium sacchari. AsPS consists of catalytically active α and inactive β domains, whereas AsCPS contains βγ domains and a truncated α domain. Heterologous expression in Aspergillus oryzae and biochemical characterization of recombinant proteins demonstrated that AsCPS synthesized copalyl diphosphate and that AsPS then converted it to (-)-sandaracopimaradiene. Since AsPS and AsCPS have distinct domain organizations from those of known fungal TCs and are likely generated through fusion or loss of catalytic domains, our findings provide insight into the evolution of TCs in fungi.
摘要：
拉普丹相关的二萜（LRD）在真菌是一种重要的药物，但未开发的天然产品家族。在真菌LRD的生物合成中，由αβγ结构域组成的双功能萜烯环化酶(TC)通常用于合成LRD的多环骨架。在这里，我们在真菌基因组数据库中进行了LRD的基因组挖掘，并确定了一对独特的TC，AsPS和AsCPS,在真菌糖精中。AsPS由催化活性α和非活性β结构域组成，而AsCPS包含βγ结构域和截短的α结构域。米曲霉中的异源表达和重组蛋白的生化表征表明，AsCPS合成了联酰二磷酸，然后AsPS将其转化为（-）-sandaracopimardiene。由于AsPS和AsCPS具有与已知真菌TC不同的域组织，并且可能是通过融合或催化结构域的丢失而产生的，我们的发现为真菌中TC的进化提供了见解。
