Biosynthetic gene cluster of bioactive natural products from marine invertebrates

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02581
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Hokkaido University
• Principal Investigator: WAKIMOTO Toshiyuki 北海道大学, 薬学研究院, 教授 (70363900)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 生合成 / 遺伝子クラスター / 海洋無脊椎動物

Outline of Final Research Achievements

Marine sponges are sessile animals harboring vast array of symbiont microorganisms. They inhabit in global oceans and the number of species are estimated to be 10,000. More than 20,000 bioactive natural products have been isolated from the marine sponges thus far. The search based on the randam screening is so common that cytotoxic compounds has been dominated and some of them exhibit significantly potent cytotoxicity with pM range of concentration. However, due to the scarcity and highly complex structure, most of them had not been developed to clinically useful anti-cancer agents. On the other hand, it has been suggested that many sponge-derived cytotoxins are produced by symbiont bacteria. In this study, we implanted the search for biosynthetic gene cluster of sponge-derived bioactive molecules and detailed analysis of biosynthetic pathway, and identification of producer symbiont.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

二次代謝産物生合成遺伝子は生合成経路の詳細にとどまらず、生物活性天然物の起源や分布を高感度に解析するための重要な研究ツールである。さらに近年では、希少生物資源に依存しない合成生物学的な物質生産系の構築が可能になりつつあり、生合成遺伝子の有用性がさらに高まっている。特に海洋生物にはアクセスや栽培、培養が困難な生物資源が多いため、海洋天然物を基にした医薬品開発において、生合成遺伝子取得の意義は極めて高い。稀少かつ医薬品資源として有望な海洋無脊椎動物由来生理活性物質の生合成遺伝子および生産菌を同定し、可培養化や異種生産を目指した基礎的知見を得ることができる。