領　域　名　生物分子化学　　　

教員氏名　 原   康 雅　

研究分野　活性構造化学　

研究キーワード：天然物，植物，微生物，共培養，生物活性

最近の研究課題

１．天然資源コレクションの構築

　自然界に存在する天然資源から，これまでに多様な天然有機化合物（天然物）が単離，構造決定されてきた．そこで，私達は，植物や微生物等の天然資源を独自に収集・保存し，天然資源コレクションやその抽出物コレクションの構築を進めている．このコレクションを用いて天然物探索を実施している．

2．微生物の休眠遺伝子活性化

　微生物のもつ天然物産生に関与する生合成遺伝子は，その多くが休眠状態であることが明らかにされている．そこで，この休眠遺伝子の活性化に繋がる，様々な微生物培養法を実施・開発し，新規天然物の取得を目指している．この培養の実施・開発は，1. で示した天然資源コレクションの拡充にも繋がる．近年，私達は動物細胞存在下での微生物の培養法による天然物探索を提唱し，微生物のみの培養では産生されない新規天然物を見出した．

３．新規天然物や生物活性天然物の探索

　1. および2. で構築した天然資源コレクションを，がんや関節リウマチ，感染症などを標的とした多様な生物活性試験や，TLCやHPLCなどによる網羅的分析を用いてスクリーニングする．その後，対象とした天然資源抽出物を分離・精製し，新規天然物や生物活性天然物の単離・構造決定を進めている．単離した天然物については，その機能解明や生合成遺伝子の推定等を試みている．

代表的な研究業績

• Hara, Y. et al. Dehydropropylpantothenamide isolated by a co-culture of Nocardia tenerifensisIFM 10554^T in the presence of animal cells. J. Nat. Med. 72, 280-289 (2018).
• Hara, Y. et al. Coculture of a pathogenic actinomycete and animal cells to produce nocarjamide, a cyclic nonapeptide with Wnt signal-activating effect. Org. Lett. 20, 5831-5834 (2018).
• Hara, Y. et al. Acacienone, a terpenoid‑like natural product having an unprecedented C20 framework isolated from Acacia mangium leaves. J. Nat. Med. 75, 99-104 (2021).
• Hara, Y. et al. Isolation of ikahonone, 4-methyl-2,4-dihydroxy-3-pentanone from Bacillus cereus IFM12235. Heterocycles 105, 523-531 (2022).
• Hara, Y. et al. Two bioactive compounds, uniformides A and B, isolated from a culture of Nocardia uniformis IFM0856^T in the presence of animal cells. Org. Lett. 24, 5867 and  4998-5002 (2022).

Research Area:　Biological Molecular Chemistry　

Research Specialization:　Natural Products Chemistry　

Name:　HARA, Yasumasa

Key words：natural products，plant, microorganism, biological activity

Recent Research

１．Establishment of natural resource collection

We collect natural resources such as plants and microorganisms, and establish natural resource collections and the extract collections. We search for new natural products from these collection.

2．Activation of microbial biosynthetic genes

 Many of the biosynthetic genes involved in the production of natural products in microorganisms are cryptic or silent. Therefore, we conduct and develop various microbial culture methods that lead to the activation of these genes in order to obtain new natural products.

 Recently, we suggested a new method to search for natural products by culturing microorganisms in the presence of animal cells.

３．Search for new natural products and bioactive natural products

　The collected natural resources are screened by various biological activity tests and  analysis by TLC and HPLC. We isolate new natural products and biologically active natural products　from selected natural resources. Also, we try to elucidate the functions and estimate the biosynthetic genes of the isolated compounds.

Publications

• Hara, Y. et al. Dehydropropylpantothenamide isolated by a co-culture of Nocardia tenerifensisIFM 10554^T in the presence of animal cells. J. Nat. Med. 72, 280-289 (2018).
• Hara, Y. et al. Coculture of a pathogenic actinomycete and animal cells to produce nocarjamide, a cyclic nonapeptide with Wnt signal-activating effect. Org. Lett. 20, 5831-5834 (2018).
• Hara, Y. et al. Acacienone, a terpenoid‑like natural product having an unprecedented C20 framework isolated from Acacia mangium leaves. J. Nat. Med. 75, 99-104 (2021).
• Hara, Y. et al. Isolation of ikahonone, 4-methyl-2,4-dihydroxy-3-pentanone from Bacillus cereus IFM12235. Heterocycles 105, 523-531 (2022).
• Hara, Y. et al. Two bioactive compounds, uniformides A and B, isolated from a culture of Nocardia uniformis IFM0856^T in the presence of animal cells. Org. Lett. 24, 5867 and  4998-5002 (2022).

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