Complete Biosynthetic Pathway of Anditomin: Nature鈥檚 Sophisticated Synthetic Route to a Complex Fungal Meroterpenoid
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- 作者：Yudai Matsuda ; Toshiyuki Wakimoto ; Takahiro Mori ; Takayoshi Awakawa ; Ikuro Abe
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：October 29, 2014
- 年：2014
- 卷：136
- 期：43
- 页码：15326-15336
- 全文大小：622K
- ISSN：1520-5126
文摘
Anditomin and its precursors, andilesins, are fungal meroterpenoids isolated from Aspergillus variecolor and have unique, highly oxygenated chemical structures with a complex bridged-ring system. Previous isotope-feeding studies revealed their origins as 3,5-dimethylorsellinic acid and farnesyl pyrophosphate and suggested the possible involvement of a Diels鈥揂lder reaction to afford the congested bicyclo[2.2.2]octane core structure of andilesins. Here we report the first identification of the biosynthetic gene cluster of anditomin and the determination of the complete biosynthetic pathway by characterizing the functions of 12 dedicated enzymes. The anditomin pathway actually does not employ a Diels鈥揂lder reaction, but involves the nonheme iron-dependent dioxygenase AndA to synthesize the bridged-ring by an unprecedented skeletal reconstruction. Another dioxygenase, AndF, is also responsible for the structural complexification, generating the end product anditomin by an oxidative rearrangement.