Development of bioactive compounds by activation of cryptic genes based on invasive evolution of pathogenic microorganisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02639
• 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: Keio University
• Principal Investigator: Arai Midori 慶應義塾大学, 理工学部(矢上), 教授 (40373261)
• Co-Investigator(Kenkyū-buntansha): 齋藤 駿 慶應義塾大学, 理工学部(矢上), 講師 (20846117)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 休眠遺伝子 / 天然物 / 共培養 / 病原真菌 / 免疫抑制作用

Outline of Final Research Achievements

We developed a method for co-culturing pathogenic microorganisms and animal cells and succeeded in activating silent genes in microorganisms. This new method imitates a pseudo-infection state. We co-cultured immune cells and pathogenic fungi isolated from clinical specimens under various conditions and discovered co-culture-specific compounds. Interestingly, several co-culture-specific compounds were found to exhibit immunosuppressive effects. We applied this co-culture method not only to pathogenic bacteria, but also to koji mold, which produces sake and miso, heat-resistant mold, and lactic acid bacteria, and found that each of them can produce co-culture-specific compounds. We also conducted research to elucidate the production mechanism and obtained some interesting findings.

Free Research Field

天然物化学，ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

放線菌や真菌は，多くの有用な化合物を提供してきた．しかしながらその遺伝子は２割程度しか働いておらず，新たな新規天然物を生産するであろう生合成遺伝子が眠ったままの休眠遺伝子であることがわかっている．したがって，この休眠遺伝子を活性化する新規な方法が熱望されており，本研究で開発した動物細胞と真菌の共培養法での新規天然物の取得は，学術的意義が大変高い．また，得られた天然物は免疫抑制作用を持つものも多く，自己免疫疾患や，免疫異常が含まれる多発性硬化症の治療薬など，多くの難病の医薬シードになり得るため，社会的意義も大変，大きいと考えられる．