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 journalArticlepeer-review

114 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

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