title: Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids.
abstract: The 6,6-quinolone scaffold of the viridicatin-type of fungal alkaloids are found in various quinolone alkaloids which often exhibit useful biological activities. Thus, it is of interest to identify viridicatin-forming enzymes and understand how such alkaloids are biosynthesized. Here an Aspergillal gene cluster responsible for the biosynthesis of 4'-methoxyviridicatin was identified. Detailed in vitro studies led to the discovery of the dioxygenase AsqJ which performs two distinct oxidations: first desaturation to form a double bond and then monooxygenation of the double bond to install an epoxide. Interestingly, the epoxidation promotes non-enzymatic rearrangement of the 6,7-bicyclic core of 4'-methoxycyclopenin into the 6,6-quinolone viridicatin scaffold to yield 4'-methoxyviridicatin. The finding provides new insight into the biosynthesis of the viridicatin scaffold and suggests dioxygenase as a potential tool for 6,6-quinolone synthesis by epoxidation of benzodiazepinediones.
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan).
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Fumi
authors.initials: F
authors.lastname: Koyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D055162:Biocatalysis; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism*; D049308:Dioxygenases / Q000378:metabolism*; D005658:Fungi / Q000737:chemistry*; D006912:Hydroxyquinolines / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D001643:Bridged Bicyclo Compounds; D006912:Hydroxyquinolines; D015363:Quinolones; C009673:viridicatin; D049308:Dioxygenases
keywords: alkaloids; enzymes; gene expression; natural products; oxidations