Genome mining of rare microbial strains for natural drug resources

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02635
• 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): 2021-04-01 – 2024-03-31
• Keywords: 生合成遺伝子

Outline of Final Research Achievements

In this study, the genome sequences of rare bacterial strains obtained by in situ culture and other methods were analysed, and the strains selected based on information on biosynthetic gene clusters were searched for new natural products using both biological activity and LC-MS profiles. As a result, several peptide-related compounds were found in strains of the genus Variovorax isolated from Hokkaido University campus soil. Furthermore, a calyculin biosynthesis gene was found in the genome of a strain of the phylum Acidobacteria, and calyculins were isolated for the first time from organisms other than marine sponges. Furthermore, a new silent gene activation method was developed using extracellular membrane vesicles (MVs) produced by bacteria.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究では従来の天然物探索事例の少ない微生物株についてゲノム情報を取得し、ゲノム情報を起点とした新規天然物の探索を実施した。その結果、物質生産に秀でたグラム陰性菌から新規のシデロフォアを見出した。さらに北海道大学キャンパスより取得した菌株より銅をキレートすることによって抗菌活性を示す天然物を取得した。さらに難培養でありながら、物質生産に長けたAcidobacteria菌株よりカリクリン類を単離し、新たな休眠遺伝子活性化手法として細胞外膜小胞を利用した手法を確立した。今後はこれらの手法をさらに発展させ、より効果的で汎用性の高い手法を確立する。