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Overexpressing Transcriptional Regulator in Aspergillus oryzae Activates a Silent Biosynthetic Pathway to Produce a Novel Polyketide
Author(s) -
Nakazawa Takehito,
Ishiuchi Kan'ichiro,
Praseuth Alex,
Noguchi Hiroshi,
Hotta Kinya,
Watanabe Kenji
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200107
Subject(s) - polyketide , gene cluster , polyketide synthase , aspergillus oryzae , biology , gene , natural product , genome , heterologous expression , context (archaeology) , biosynthesis , heterologous , computational biology , genetics , enzyme , biochemistry , recombinant dna , paleontology
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.