Advancement of resources for drug discovery seeds utilizing microbial interactions and elucidation of activation mechanism of microbial dormant gene clusters

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21222
• Project/Area Number (Other): 18H06102 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Chiba University
• Principal Investigator: Yasumasa Hara 千葉大学, 大学院薬学研究院, 助教 (10824625)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 共培養 / 微生物資源 / 培養抽出物ライブラリー構築 / 海洋由来真菌 / ミコール酸含有細菌 / 放線菌

Outline of Final Research Achievements

Co-culture experiments using marine-derived Aspergillus niger with Mycobacterium smegmatis, a mycolic acid-containing bacteria resulted in the production of a pigment by A. niger and increased cytotoxic activity of the extract against human prostate cancer cells. An analysis of secondary metabolites in the extract of the co-culture broth revealed that the increase in cytotoxic activity was caused by the production of malformin C, and that TMC-256A1, desmethylkotanin, and aurasperone C were selectively produced under co-culture conditions. In addition, further study suggested that direct interaction between the two microorganisms was necessary for the production of the pigment and the cytotoxic compound malformin C from A. niger.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、研究例が少ない真菌とミコール酸含有細菌の共培養は、真菌の休眠遺伝子を活性化し新たな天然物を探索する方法になると考えられ、医薬シード探索資源の高度化につながる可能性がある。また、本研究成果より得られた共培養による休眠遺伝子活性化メカニズムに関する知見は、今後、汎用性の高い休眠遺伝子活性化法の確立や自然界における二次代謝産物の産生意義の解明の糸口につながるものと期待する。