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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Angelica O
authors.initials: AO
authors.lastname: Zabala
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yit-Heng
authors.initials: YH
authors.lastname: Chooi
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001234:Aspergillus niger / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D001578:Benzopyrans / Q000737:chemistry; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D006900:Hydroxylation; D005810:Multigene Family; D010860:Pigments, Biological / Q000096:biosynthesis* / Q000737:chemistry; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D005656:Fungal Proteins; D010860:Pigments, Biological; D011714:Pyrans; D011994:Recombinant Proteins; C494154:azaphilone; D048630:Polyketide Synthases