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

Abstract

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.

Spectasterols, Aromatic Ergosterols with 6/6/6/5/5, 6/6/6/6, and 6/6/6/5 Ring Systems from Aspergillus spectabilis

“…Aspergillus sp. are recognized for their biosynthetic capacities and produce secondary metabolites such as polyketides, alkaloids, terpenoids, steroids, and anthraquinone. − In a previous study on Aspergillus spectabilis, we isolated and characterized a series of sesterterpenoids . As a continuation of this work, five aromatic ergosterols, spectasterols A–E ( 1 – 5 ), were isolated, which have carbon skeletons that were possibly derived via additional cyclization ( 1 and 2 ) or pinacol rearrangements ( 3 , 4 , and 5 ).…”

Genome Mining of α-Pyrone Natural Products from Ascidian-Derived Fungus Amphichordafelina SYSU-MS7908

“…Zhu et al [ 4 ] expressed a cryptic BGC from Trichoderma harzianum t-22 in Aspergillus nidulans A1145 and successfully isolated several tetronate natural products, such as trihazone A–F. Similarly, Li et al [ 5 ] characterized a cryptic BGC from A. hancockii in A. nidulans LO8030 and discovered a metabolite with a unique prenylated 6/6/6/5 tetracarbocyclic skeleton. The quadruple auxotroph A. oryzae NSAR1 is also a frequently-used heterologous host for genome mining of fungal natural products.…”

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“…Genome mining and activation of a cryptic polyketide synthase gene from Aspergillus hancockii has allowed the discovery of hancockinone A 30 , a prenylated polycyclic aromatic polyketide with a 6/6/6/5 skeleton. 22 The cytochrome P450 enzyme HknE was shown to catalyse oxidative cyclisation of the precursor, neosartorcin B, yielding the cyclopentenone ring of 30 .…”