Journal
ORGANIC LETTERS
Volume 23, Issue 22, Pages 8789-8793Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.1c03283
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Funding
- Australian Research Council [FT160100233, DP210102180, CRCPFIVE000119]
- Australian Research Council [FT160100233] Funding Source: Australian Research Council
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Activation of a cryptic polyketide synthase gene cluster hkn from Aspergillus hancockii by overexpressing the gene-cluster-specific transcription factor HknR led to the discovery of a novel polycyclic metabolite named hancockinone A. This compound, featuring a unique prenylated tetracyclic skeleton, exhibits moderate antibacterial activity and the role of cytochrome P450 HknE in constructing the five-membered ring in hancockinone A has been confirmed through heterologous expression, substrate feeding, and in vitro assays.
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.
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