title: Overexpressing transcriptional regulator in Aspergillus oryzae activates a silent biosynthetic pathway to produce a novel polyketide.
abstract: Fungal genomes carry many gene clusters seemingly capable of natural product biosynthesis, yet most clusters remain silent. This places a major constraint on the conventional approach of cloning these genes in more amenable heterologous host for the natural product biosynthesis. One way to overcome this difficulty is to activate the silent gene clusters within the context of the target fungus. Here, we successfully activated a silent polyketide biosynthetic gene cluster in Aspergillus oryzae by overexpressing a transcriptional regulator found within the cluster from a plasmid. This strategy allowed us to isolate a new polyketide product and to efficiently decipher its biosynthetic pathway. Through this exercise, we also discovered unexpected activities of the biosynthetic enzymes found in the cluster. These results indicate that our approach would be valuable for isolating novel natural products and engineering analogues of comparable, if not more potent, bioactivity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Kan'ichiro
authors.initials: K
authors.lastname: Ishiuchi
authors.forename: Alex
authors.initials: A
authors.lastname: Praseuth
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D001236:Aspergillus oryzae / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005810:Multigene Family; D061065:Polyketides / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D061065:Polyketides; D014157:Transcription Factors