Complete Biosynthetic Pathway of Anditomin: Nature’s Sophisticated Synthetic Route to a Complex Fungal Meroterpenoid

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 pyro...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2014-10, Vol.136 (43), p.15326-15336
Main Authors: Matsuda, Yudai, Wakimoto, Toshiyuki, Mori, Takahiro, Awakawa, Takayoshi, Abe, Ikuro
Format: Article
Language:English
Subjects:
Aspergillus - enzymology
Aspergillus - genetics
Aspergillus - metabolism
Computational Biology
Multigene Family
Oxidation-Reduction
Sesterterpenes - chemistry
Sesterterpenes - metabolism
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Summary: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–Alder 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–Alder 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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja508127q