期刊
CHEMBIOCHEM
卷 13, 期 6, 页码 855-861出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201200107
关键词
gene expression; genome mining; metabolic pathway identification; polyketides; transcriptional regulator
资金
- Japan Society for the Promotion of Science (JSPS) [LS103]
- New Energy and Industrial Technology Development Organization (NEDO) of Japan [09C46 001a]
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Takeda Science Foundation
- Noda Institute for Scientific Research
- Grants-in-Aid for Scientific Research [23880025, 23406031, 22241054] Funding Source: KAKEN
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.
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