Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases
Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases
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DOI：
10.1038/nchem.764
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发表时间：
2010-10-01
期刊：
影响因子：
21.8
通讯作者：
Kushiro, Tetsuo
中科院分区：
文献类型：
--
作者：
Itoh, Takayuki;Tokunaga, Kinya;Kushiro, Tetsuo
类萜化合物是萜类化合物和聚酮化合物来源的混合天然产物。我们确定了一个生物合成基因簇，负责生产的部分萜类啶南平在真菌烟曲霉通过重建生物合成的异源真菌表达系统中的多达五个步骤。该簇揭示了一种以前未知的萜烯环化酶，具有不寻常的序列和蛋白质一级结构。该序列在其他部分萜类和吲哚-二萜生物合成基因簇中的广泛出现表明这些酶参与真菌和细菌产生的各种萜类代谢产物的生物合成。此外，一种新的聚酮合酶，将烟酰辅酶A作为起始单元和异戊烯基转移酶，类似于泛醌生物合成，被发现参与啶南平的生物合成。啶南平类似物的成功生产说明了这些酶用于生产具有有用生物活性的新型类似物的催化多功能性。
Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.