Genome Mining of Aspergillus hancockii Unearths Cryptic Polyketide Hancockinone A Featuring a Prenylated 6/6/6/5 Carbocyclic Skeleton

Org Lett. 2021 Nov 19;23(22):8789-8793. doi: 10.1021/acs.orglett.1c03283. Epub 2021 Nov 8.


Activation of a cryptic polyketide synthase gene cluster hkn from Aspergillus hancockii via overexpression of the gene-cluster-specific transcription factor HknR led to the discovery of a novel polycyclic metabolite, which we named hancockinone A. The compound features an unprecedented prenylated 6/6/6/5 tetracarbocyclic skeleton and shows moderate antibacterial activity. Heterologous expression, substrate feeding, and in vitro assays confirmed the role of cytochrome P450 HknE in constructing the five-membered ring in hancockinone A from the precursor neosartoricin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Polyketides*


  • Polyketides