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Title: Overexpressing Transcriptional Regulator in Aspergillus oryzae Activates a Silent Biosynthetic Pathway to Produce a Novel Polyketide
Authors: Nakazawa, T.
Ishiuchi, K.
Praseuth, A.
Noguchi, H.
Hotta, K. 
Watanabe, K.
Keywords: Gene expression
Genome mining
Metabolic pathway identification
Transcriptional regulator
Issue Date: Apr-2012
Citation: Nakazawa, T., Ishiuchi, K., Praseuth, A., Noguchi, H., Hotta, K., Watanabe, K. (2012-04). Overexpressing Transcriptional Regulator in Aspergillus oryzae Activates a Silent Biosynthetic Pathway to Produce a Novel Polyketide. ChemBioChem 13 (6) : 855-861. ScholarBank@NUS Repository.
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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: ChemBioChem
ISSN: 14394227
DOI: 10.1002/cbic.201200107
Appears in Collections:Staff Publications

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