Producing the luminamicin analogs by genetic engineering

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Kitasato University
• Principal Investigator: Inahashi Yuki 北里大学, 感染制御科学府, 准教授 (70645522)
• Co-Investigator(Kenkyū-buntansha): 廣瀬 友靖 北里大学, 感染制御科学府, 教授 (00370156) ; 松井 秀仁 北里大学, 大村智記念研究所, 講師 (80503797)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ルミナミシン / Clostridioides difficile / 生合成 / 放線菌

Outline of Final Research Achievements

The biosynthetic gene cluster of luminamicin, an anti C. difficile agent, was predicted from the genome sequence of OMR-59. The deletion mutant of each gene, which may involve the coupling of the northern and southern parts, was generated. The LC/UV analysis of the metabolites indicated that those genes were important for the biosynthesis. Furthermore, the intermediates (or shunt products) of luminamicin biosynthesis were isolated from the culture broths. We evaluated the antibiotic activity of those compounds against C. difficile, but they did not have the activity. This result gave the information of structure and activity relationship.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

ルミナミシンは放線菌Streptomyces sp. OMR-59の培養液より発見された強力かつ選択性に優れた抗C. difficile活性物質である。本研究よりルミナミシンの生合成遺伝子クラスターが特定され、いくつかの遺伝子についてその機能が推定された。また、取得されたルミナミシン類縁体より僅かではあるが構造活性相関の情報が得られた。今後、本研究より得られた結果を基に、遺伝子組換え株からの類縁体取得やその誘導化を行い、より活性の強いルミナミシン類縁体の取得が期待される。