Studies on the macrocyclization in the biosynthesis of fungal ribosomal peptides

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15263
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry
• Research Institution: Hokkaido University
• Principal Investigator: Ozaki Taro 北海道大学, 理学研究院, 助教 (40709060)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 生合成

Outline of Final Research Achievements

The biosynthetic genes for fungal ribosomal peptides are widely distributed among fungal genomes and expected to be a rich source of biologically active compounds. However, the genomic information has not been utilized well, possibly due to the lack of information about their biosynthetic pathway. In this study, the biosynthetic pathway of fungal ribosomal peptides, especially focusing on macrocyclization, were analyzed. The biosynthetic genes for asperpin-2a, a bicyclic ribosomal peptide, were cloned and expressed in the heterologous host Aspergillus oryzae. As a result, asperipin-2a was successfully produced by the transformant. This result indicated that the macrocyclization in the asperipin-2a biosynthesis proceed in a similar manner to that of ustiloxin B. Because the number of genes involved in macrocyclization of asperipin-2a was smaller than that in the biosynthesis of ustiloxin B, this finding may facilitate the characterization of this intriguing process in detail.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

糸状菌のゲノムには、リボソームペプチドの生合成遺伝子が数多く見出される。生合成経路の詳細な解析例はustiloxin Bの一例のみであり、利用は進んでいないのが現状である。本研究でasperipin-2a生合成経路の異種宿主内での再構築に成功した。さらに、異種宿主から調製した化合物を使い、本化合物の絶対配置の決定に成功した。これにより環化反応が立体選択的に進行することが示唆された。Ustiloxin Bと比較して環化に関与する遺伝子の数が少ないことから、今後本化合物を材料として解析を進めることで、環化酵素の解析が容易になると期待される。