title: Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis.
abstract: Austinol, a fungal meroterpenoid derived from 3,5-dimethylorsellinic acid, has a unique chemical structure with a remarkable spiro-lactone ring system. Despite the recent identification of its biosynthetic gene cluster and targeted gene-deletion experiments, the process for the conversion of protoaustinoid A (2), the first tetracyclic biosynthetic intermediate, to the spiro-lactone preaustinoid A3 (7) has remained enigmatic. Here we report the mechanistic details of the enzyme-catalyzed, stereospecific spiro-lactone ring-forming reaction, which is catalyzed by a non-heme iron-dependent dioxygenase, AusE, along with two flavin monooxygenases, the 5'-hydroxylase AusB and the Baeyer-Villiger monooxygenase AusC. Remarkably, AusE is a multifunctional dioxygenase that is responsible for the iterative oxidation steps, including the oxidative spiro-ring-forming reaction, to produce the austinol scaffold.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Awakawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D001236:Aspergillus oryzae / Q000201:enzymology; D055162:Biocatalysis; D049308:Dioxygenases / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry*; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D013141:Spiro Compounds; D013729:Terpenes; C573071:austinol; D049308:Dioxygenases