Reactive Azlactone Intermediate Drives Fungal Secondary Metabolite Cross-Pathway Generation

J Am Chem Soc. 2023 Feb 8;145(5):3221-3228. doi: 10.1021/jacs.2c13188. Epub 2023 Jan 27.


Pathogenic fungi of Aspergillus section Fumigati are known to produce various secondary metabolites. A reported isolation of a compound with an atypical carbon skeleton called fumimycin from A. fumisynnematus prompted us to examine a related fungus, A. lentulus, for production of similar products. Here we report the isolation of fumimycin and a related new racemic compound we named lentofuranine. Detailed analyses revealed that both compounds were assembled by a nonenzymatic condensation of a polyketide intermediate from the terrein biosynthetic pathway and a highly reactive azlactone intermediate produced by an unrelated nonribosomal peptide synthetase carrying a terminal condensation-like domain. While highly reactive azlactone is commonly used in chemical synthesis, its production by a conventional non-metalloenzyme and employment as a biosynthetic pathway intermediate is unprecedented. The observed unusual carbon skeleton formation is likely due to the reactivity of azlactone. Our finding provides another example of a chemical principle being aptly exploited by a biological system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus* / metabolism
  • Carbon* / metabolism


  • Carbon