Search for bioactive substances from uncultured microorganisms

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16394
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Hiroshima University
• Principal Investigator: YAMANO YOSHI 広島大学, 医系科学研究科(薬), 助教 (70650597)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 難培養性微生物 / 難培養微生物 / 天然物 / 生物活性物質

Outline of Final Research Achievements

This research was conducted with the aim of establishing a method to use "difficult-to-culture microbes" as a new source for drug discovery. Despite the importance of these microbes as sources for drug discovery, they had not been utilized previously due to the challenges associated with their cultivation.　　A key accomplishment of the study was the creation of the Gichip, a device that enables the isolation and cultivation of microbes under conditions similar to their natural environment. Using the Gichip, dozens of new microbial species were isolated. Whole genome analysis was performed on the isolated bacterial strains, and their potential to produce chemical compounds was assessed.
LC-MS/MS analysis of the microbial cultures was used as a benchmark for the search for new compounds. As a result, a new diketopiperazine compound and a new bianthracene compound were each isolated and structurally analyzed from two different strains.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、数多くの新規微生物を分離培養し、その全ゲノム解析を行った。この研究成果から、医薬品探索源としての新規微生物の利用が可能となり、またそのゲノム配列からは未知の化合物や難培養性関連因子の情報を抽出できることから、これらの成果が幅広い研究分野の進展に寄与することが期待される。探索源としての新規微生物は既知・新規の両方の化合物を産生するため、既知化合物の再単離という非効率な結果をもたらすことも予測されるが、本研究ではLC-MS/MS分析を利用し、新規化合物を選択的に単離する手法を確立した。これにより、難培養性微生物から医薬品候補化合物を効率的に取得する研究手法の確立に向けて大きく前進した。