Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids

Angew Chem Int Ed Engl. 2014 Nov 17;53(47):12880-4. doi: 10.1002/anie.201407920. Epub 2014 Sep 22.


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.

Keywords: alkaloids; enzymes; gene expression; natural products; oxidations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Biocatalysis*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / metabolism*
  • Dioxygenases / metabolism*
  • Fungi / chemistry*
  • Hydroxyquinolines / chemistry
  • Hydroxyquinolines / metabolism*
  • Molecular Structure
  • Oxidation-Reduction
  • Quinolones / chemistry
  • Quinolones / metabolism*


  • Alkaloids
  • Bridged Bicyclo Compounds
  • Hydroxyquinolines
  • Quinolones
  • viridicatin
  • Dioxygenases