Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation

A.O. Zabala, W. Xu, Heng Chooi, Y. Tang

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. Although widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we discovered six azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly reducing PKS and a non-reducing PKS. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. © 2012 Elsevier Ltd.
Original languageEnglish
Pages (from-to)1049-1059
JournalChemistry and Biology
Volume19
Issue number8
DOIs
Publication statusPublished - 2012

Fingerprint

Polyketide Synthases
Pyrans
Hydroxylation
Aspergillus niger
Aspergillus
Multigene Family
Genes
Biosynthesis
Biosynthetic Pathways
Metabolites
Mixed Function Oxygenases
Bioactivity
Fungi
Chemical activation
azaphilone

Cite this

@article{9c87dd5381184b2899e9d3e8beac95d6,
title = "Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation",
abstract = "Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. Although widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we discovered six azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly reducing PKS and a non-reducing PKS. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. {\circledC} 2012 Elsevier Ltd.",
author = "A.O. Zabala and W. Xu and Heng Chooi and Y. Tang",
year = "2012",
doi = "10.1016/j.chembiol.2012.07.004",
language = "English",
volume = "19",
pages = "1049--1059",
journal = "Chemistry & Biology",
issn = "1074-5521",
publisher = "Cell Press",
number = "8",

}

Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation. / Zabala, A.O.; Xu, W.; Chooi, Heng; Tang, Y.

In: Chemistry and Biology, Vol. 19, No. 8, 2012, p. 1049-1059.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation

AU - Zabala, A.O.

AU - Xu, W.

AU - Chooi, Heng

AU - Tang, Y.

PY - 2012

Y1 - 2012

N2 - Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. Although widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we discovered six azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly reducing PKS and a non-reducing PKS. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. © 2012 Elsevier Ltd.

AB - Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. Although widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we discovered six azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly reducing PKS and a non-reducing PKS. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. © 2012 Elsevier Ltd.

U2 - 10.1016/j.chembiol.2012.07.004

DO - 10.1016/j.chembiol.2012.07.004

M3 - Article

VL - 19

SP - 1049

EP - 1059

JO - Chemistry & Biology

JF - Chemistry & Biology

SN - 1074-5521

IS - 8

ER -