2020 Fiscal Year Final Research Report
Study on the synthetic biological approach toward fermentative production of rare-natural products from unculturable and symbiotic microorganisms
Project/Area Number |
19K15744
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 38020:Applied microbiology-related
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Research Institution | National Institute of Advanced Industrial Science and Technology |
Principal Investigator |
Kudo Kei 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (80828161)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | 難培養性微生物 / 合成生物学 / 天然物化学 / 海洋天然物 / ゲノム解析 / 異種発現 / 抗がん剤 |
Outline of Final Research Achievements |
The researcher sequenced the genomes of safracin- or saframycin-producing microorganism. The biosynthetic gene cluster of each compound was annotated and successfully cloned into a BAC vector. The BAC containing safracin gene cluster was introduced into a host organism, Pseudomonas putida, resulting in the production of safracin heterologously. Then, the researcher employed a conditional expression system to raise the production yield. By comparing the genome sequences between the ET-743 producer, an unculturable and symbiotic microorganism, and the safracin producer, the researcher deduced several unique genes not found in the safracin cluster but the ET-743 cluster. Those candidates were prepared as synthetic DNAs and assembled into an artificial operon. The addition of the artificial operon into the safracin producing system did not give any new compounds as expected.
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Free Research Field |
天然物化学
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Academic Significance and Societal Importance of the Research Achievements |
構築したsafracin異種生産系においては、safracin以外の生合成中間体と思われる化合物ピークが多数観察されたことから、本システムを利用した多様性創出が可能であることが示唆された。一方で、safracin類はDNA損傷を引き起こす薬剤であるため、生産宿主にとっても毒性を発揮する。そのような化合物の高生産に、条件発現系が有効であることが明らかになった。また、単に難培養微生物由来の公開ゲノム配列から抽出した遺伝子配列を用いるのではなく、導入した各遺伝子の発現解析や、ゲノム情報の正確性について吟味することの必要性が今後の課題として明白となった。
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