Isolation and structure determination of new lasso peptides based on genome mining

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K01913
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Shizuoka University
• Principal Investigator: Kodani Shinya 静岡大学, 農学部, 准教授 (20510621)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ペプチド / 微生物生産 / 発酵

Outline of Final Research Achievements

The Lasso peptide is a kind of cyclic peptide, and it is known to exert various pharmacological activities. In this study, we screened for new lasso peptides using genetic information (genome mining) and succeeded in obtaining many new lasso peptides mainly from actinomycetes. We also worked on the development of a heterologous production method using a soil bacterium Sphingomonas as a host, and succeeded in producing the new lasso peptide named brevunsin. The obtained rasso peptide was subjected to structure determination using NMR and ESI-MS, and the three-dimensional three-dimensional structure was successfully determined based on the NOE experiments.

Free Research Field

応用微生物学

Academic Significance and Societal Importance of the Research Achievements

現在、分子量2000程度のペプチドは中分子として次世代医薬品のターゲットとして注目されている。本研究課題においては、バクテリアの生産する特殊な構造を有するラッソペプチドの生産および構造決定に成功した。また、その中で抗菌活性、抗HIV活性など有用な活性を有するものを複数発見することができた。また、スフィゴモナス属細菌をホストに用いた異宿主生産システムの開発にも成功しており、組み換えペプチドの生産にも期待が持てる。