Development of innovative natural product producing methods based on large-scale genome editing system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19324
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Tohoku University
• Principal Investigator: Asai Teigo 東北大学, 薬学研究科, 教授 (60572310)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 天然物化学 / 糸状菌 / 生合成 / ゲノム再編成

Outline of Final Research Achievements

Fungi have a huge number of untapped silent biosynthetic gene clusters. In this study, we attempted to develop a method to activate untapped silent biosynthetic gene clusters in fungi by applying a large-scale genome editing technique induced by DNA cleavage with restriction enzymes, with the aim of developing a new method to search for new compounds. After expressing restriction enzymes in Aspergillus niger and cultivated under various conditions. Finally, we found that some mutant strains that shows different morphologies could be obtained by continuing cultivation under around 30 degrees Celsius. We observed that some mutants showed the different secondary metabolite profiles from that of the parental strain. Genome analysis of those mutants suggested the presence of genome editing by restriction enzyme. Although the results are currently preliminal, they show that genome reorganization can be used to activate a wide variety of dormant genes.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

天然物は様々な医薬品開発に貢献してきた重要な医薬資源である。感染症治療薬の分野では顕著な貢献をしており、新規天然物の発見が、新規医薬品の開発を支えてきた。本研究は、糸状菌のゲノム上に存在する未知天然物の生産を誘導することを可能にする技術の開発であり、本研究に端を発する、新規休眠遺伝子活性化法が確立できれば、様々な糸状菌、さらには他の微生物に応用することで、これまでにはない天然物を含むスクリーニングソースの構築が可能になり、新しい作用を示す医薬品の探索を加速させることが期待される。