Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton

Hang Li; Si Shu; John A. Kalaitzis; Zhuo Shang; Daniel Vuong; Andrew Crombie; Ernest Lacey; Andrew M. Piggott; Yit-Heng Chooi

doi:10.1021/acs.orglett.1c03283

Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton

Hang Li^*, Si Shu, John A. Kalaitzis, Zhuo Shang, Daniel Vuong, Andrew Crombie, Ernest Lacey, Andrew M. Piggott^*, Yit-Heng Chooi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	8789-8793
Number of pages	5
Journal	Organic Letters
Volume	23
Issue number	22
DOIs	https://doi.org/10.1021/acs.orglett.1c03283
Publication status	Published - 19 Nov 2021

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10.1021/acs.orglett.1c03283

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@article{f5e8d27eaef347f185f71e3dc6108a0a,

title = "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. ",

author = "Hang Li and Si Shu and Kalaitzis, {John A.} and Zhuo Shang and Daniel Vuong and Andrew Crombie and Ernest Lacey and Piggott, {Andrew M.} and Yit-Heng Chooi",

year = "2021",

month = nov,

day = "19",

doi = "10.1021/acs.orglett.1c03283",

language = "English",

volume = "23",

pages = "8789--8793",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

number = "22",

}

Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton. / Li, Hang; Shu, Si; Kalaitzis, John A.; Shang, Zhuo; Vuong, Daniel; Crombie, Andrew; Lacey, Ernest; Piggott, Andrew M.; Chooi, Yit-Heng.

In: Organic Letters, Vol. 23, No. 22, 19.11.2021, p. 8789-8793.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton

AU - Li, Hang

AU - Shu, Si

AU - Kalaitzis, John A.

AU - Shang, Zhuo

AU - Vuong, Daniel

AU - Crombie, Andrew

AU - Lacey, Ernest

AU - Piggott, Andrew M.

AU - Chooi, Yit-Heng

PY - 2021/11/19

Y1 - 2021/11/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85119416040&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/arc/FT160100233

UR - http://purl.org/au-research/grants/arc/DP210102180

U2 - 10.1021/acs.orglett.1c03283

DO - 10.1021/acs.orglett.1c03283

M3 - Article

C2 - 34747627

AN - SCOPUS:85119416040

VL - 23

SP - 8789

EP - 8793

JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

IS - 22

ER -

Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton

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UWA led: CRISPR-based pathway activation for bioactive molecule discovery in fungi

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Genome mining of Aspergillus hancockii unearths cryptic polyketide hancockinone A featuring a prenylated 6/6/6/5 carbocyclic skeleton

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UWA led: CRISPR-based pathway activation for bioactive molecule discovery in fungi

BioAustralis, towards the future

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