title: Complete biosynthetic pathway of anditomin: nature's sophisticated synthetic route to a complex fungal meroterpenoid.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mori
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Awakawa
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D001230:Aspergillus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D005810:Multigene Family; D010084:Oxidation-Reduction; D054830:Sesterterpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D054830:Sesterterpenes