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 (Alex) 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 (Alex) Shang, Daniel Vuong, Andrew Crombie, Ernest Lacey, Andrew M. Piggott, Yit-Heng Chooi

School of Molecular Sciences

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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

Li, et al., 2021 Genome mining of AspergillusAccepted author manuscript, 669 KB

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CRISPR-based pathway activation for bioactive molecule discovery in fungi
Chooi, H., Piggott, A. & Keller, N.
Australian Research Council
18/01/21 → 17/01/24
Project: Research
Uncovering the Hidden Secondary Metabolite Biosynthetic Potential of Fungi
Chooi, H.
Australian Research Council
1/01/17 → 15/03/21
Project: Research

Cite this

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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 Shang, {Zhuo (Alex)} 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",

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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 (Alex)

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.

U2 - 10.1021/acs.orglett.1c03283

DO - 10.1021/acs.orglett.1c03283

M3 - Article

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EP - 8793

JO - Organic Letters

JF - Organic Letters

SN - 1523-7052

IS - 22

ER -

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

Abstract

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Projects

CRISPR-based pathway activation for bioactive molecule discovery in fungi

Uncovering the Hidden Secondary Metabolite Biosynthetic Potential of Fungi

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