Development of induced production method for dormant fungal secondary biogenesis by modulating new epigenetic targets

• Project/Area Number: 25870660
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry; Natural medicines
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: YAMAZAKI Hiroyuki 東北薬科大学, 薬学部, 助教 (70525344)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ケミカルエピジェネティクス / 休眠生合成遺伝子 / 海洋糸状菌 / 二次代謝産物 / 生物活性物質 / 新規活性物質 / 新規生物活性物質

Outline of Final Research Achievements

We have investigated the induced production of new fungal metabolites by modulating new targets of epigenetic factor and several culture methods.
In the course of our studies, the production of a bisabolane sesquiterpene from marine-derived fungus Trichoderma sp. TPU199 was induced using the fermentation with resveratrol as a sirtuin activator. Our continuous efforts revealed that the strain TPU199 had the ability to produce halogenated epidithiodiketopiperazines by the cultivation supplemented with sodium halides. Especially, NaI-added fermentation of the strain TPU199 led to the production of a new iodo derivative, iododithiobrevamide. Moreover, sixteen new metabolites were isolated from the culture broth of six fungal and one actinomycete strains obtained during this study.

Research Products

• [Int'l Joint Research] Sam Ratulangi University(インドネシア)
• [Journal Article] A dimeric urea of the bisabolene sesquiterpene from the Okinawan marine sponge Axinyssa sp. inhibits protein tyrosine phosphatase 1B activity in Huh-7 human hepatoma cells. (2016)
  • Author(s): Abdjul, D. B., Kanno, S., Yamazaki, H., Ukai, K. Namikoshi, M.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 26 Issue: 2 Pages: 315-317
  • DOI: 10.1016/j.bmcl.2015.12.022
  • Peer Reviewed
• [Journal Article] Asperdichrome, an unusual dimer of tetrahydroxanthone through an ether bond, with protein tyrosine phosphatase 1B inhibitory activity, from the Okinawan freshwater Aspergillus sp. TPU1343. (2016)
  • Author(s): Yamazaki, H., Ukai, K., Namikoshi, M.
  • Journal Title: Tetrahedron Lett. Volume: 57 Issue: 7 Pages: 732-735
  • DOI: 10.1016/j.tetlet.2015.12.111
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Penicyrones A and B, an epimeric pair of α-pyrone-type polyketides from the marine-derived Penicillium sp. (2016)
  • Author(s): Bu, Y.-Y., Yamazaki, H., Takahashi, O., Kirikoshi, R., Ukai, K., Namikoshi, M.
  • Journal Title: J. Antibiot. Volume: 69 Issue: 1 Pages: 57-61
  • DOI: 10.1038/ja.2015.82
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structures and biological activities of triterpenes and sesquiterpenes obtained from Russula lepida. (2016)
  • Author(s): Lee, J.-S., Maarisit, W., Abdjul, D.B., Yamazaki, H., Takahashi, O., Kirikoshi, R., Kanno, S., Namikoshi, M.
  • Journal Title: Phytochemistry Volume: 127 Pages: 63-68
  • DOI: 10.1016/j.phytochem.2016.03.014
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Isopetrosynol, a new protein tyrosine phosphatase 1B inhibitor, from the marine sponge Halichondria cf. panicea collected at Iriomote Island. (2016)
  • Author(s): Abdjul, D.B., Yamazaki, H., Takahashi, O., Kirikoshi, R., Ukai, K., Namikoshi, M.
  • Journal Title: Chem. Pharm. Bull. Volume: 64
  • NAID: 130005160060
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Two new indole derivatives from a marine sponge Ircinia sp. collected at Iriomote Island. (2015)
  • Author(s): Abdjul, D.B., Yamazaki, H., Ukai, K., and Namikoshi, M.
  • Journal Title: J. Nat. Med. Volume: in press Issue: 3 Pages: 416-420
  • DOI: 10.1007/s11418-015-0891-y
  • NAID: 40020494459
  • Peer Reviewed
• [Journal Article] Structures and biological evaluations of agelasines isolated from the Okinawan marine sponge Agelas nakamurai. (2015)
  • Author(s): Abdjul, D. B., Yamazaki, H., Kanno, S., Takahashi, O., Kirikoshi, R., Ukai, K., Namikoshi, M.
  • Journal Title: J. Nat. Prod. Volume: 78 Issue: 6 Pages: 1428-1433
  • DOI: 10.1021/acs.jnatprod.5b00375
  • Peer Reviewed
• [Journal Article] Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors from an Indonesian ascidian-derived Penicillium verruculosum. (2015)
  • Author(s): Yamazaki H., Nakayama, W., Takahashi, O., Kirikoshi, R., Izumikawa, R., Iwasaki, K., Toraiwa, K., Rotinsulu, H., Wewengkang, D. S., Sumilat, D. A., Mangindaan, R. E. P., Namikoshi, M.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 25 Issue: 16 Pages: 3087-3090
  • DOI: 10.1016/j.bmcl.2015.06.026
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Strongylophorines, new protein tyrosine phosphatase 1B inhibitors, from the marine sponge Strongylophora strongilata collected at Iriomote Island. (2015)
  • Author(s): Lee, J.-S., Abdjul, D. B., Yamazaki, H., Takahashi, O., Kirikoshi, R., Ukai, K., Namikoshi, M.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 25 Issue: 18 Pages: 3900-3902
  • DOI: 10.1016/j.bmcl.2015.07.039
  • Peer Reviewed
• [Journal Article] Penicillimide, an open-chain hemisuccinimide from Okinawan marine-derived Penicillium copticola. (2015)
  • Author(s): Bu, Y.-Y., Yamazaki, H., Ukai, K., and Namikoshi, M
  • Journal Title: J. Antibiot. Volume: in press Issue: 8 Pages: 537-539
  • DOI: 10.1038/ja.2015.21
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Induced production of a new unprecedented epitrithiodiketopiperazine, chlorotrithiobrevamide, by a culture of the marine-derived Trichoderma cf. brevicompactum with dimethyl sulfoxide. (2015)
  • Author(s): Yamazaki, H., Takahashi, O., Murakami, K., Namikoshi, M.
  • Journal Title: Tetrahedron Lett. Volume: 56 Issue: 45 Pages: 2319-2321
  • DOI: 10.1016/j.tetlet.2015.09.113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Induced production of halogenated epidithiodiketopiperazines by a marine-derived Trichoderma cf. brevicompactum with sodium halides. (2015)
  • Author(s): Yamazaki, H., Rotinsulu, H., Narita, R., Takahashi, R., Namikoshi, M.
  • Journal Title: J. Nat. Prod. Volume: 78 Issue: 10 Pages: 2319-2321
  • DOI: 10.1021/acs.jnatprod.5b00669
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Trichoketides A and B, two new protein tyrosine phosphatase 1B inhibitors from the marine-derived fungus Trichoderma sp. (2015)
  • Author(s): Yamazaki, H., Saito, R., Takahashi, O., Kirikoshi, R., Toraiwa, K.; Iwasaki, K., Izumikawa, Y., Nakayama, W., Namikoshi, M.
  • Journal Title: J. Antibiot. Volume: 68 Issue: 10 Pages: 628-632
  • DOI: 10.1038/ja.2015.44
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two new protein tyrosine phosphatase 1B inhibitors, hyattellactones A and B, from an Indonesian marine sponge Hyattella sp. (2015)
  • Author(s): Abdjul, D.B., Yamazaki, H., Takahashi, O., Kirikoshi, R., Mangindaan, R.E.P., and Namikoshi, M.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 25 Issue: 4 Pages: 904-907
  • DOI: 10.1016/j.bmcl.2014.12.058
  • Peer Reviewed
• [Journal Article] Absolute structures and bioactivity of euryspongins and eurydiene obtained a marine sponge Euryspongia sp. collected at Iriomote Island. (2015)
  • Author(s): Yamazaki, H., Takahashi, O., Kanno, S., Nakazawa, T., Takahashi, S., Ukai, K., Sumilat, D.A., Ishikawa, M., and Namikoshi M.
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Issue: 4 Pages: 797-802
  • DOI: 10.1016/j.bmc.2014.12.049
  • Peer Reviewed
• [Journal Article] Anti-mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A. (2014)
  • Author(s): Bu, Y.-Y., Yamazaki, H., Ukai, K., and Namikoshi, M.
  • Journal Title: Mar. Drugs Volume: 12 Issue: 12 Pages: 6102-6112
  • DOI: 10.3390/md12126102
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quest of protein tyrosine phosphatase 1B inhibitors from aquatic fungi collected in Aomori. (2014)
  • Author(s): Chida, K., Saito, R., Yamazaki, H., Kanno, S., Ishikawa, M., and Namikoshi, M.
  • Journal Title: J. Tohoku Phrarm. Univ. Volume: 61 Pages: 35-39
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] パラオ産海洋糸状菌 Trichoderma cf. brevicompactumTPU199株のジメチルスルフォキシド添加培養によるchlorotrithiobrevamideの生産誘導 (2016)
  • Author(s): 山崎寛之, 高橋央宜, 村上一輝, 浪越通夫
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] 海洋糸状菌Penicillium sp. TPU1271株が生産するポリケタイド化合物penicyrones AおよびBに関する研究 (2016)
  • Author(s): 卜 英悦, 山崎寛之, 高橋央宜, 桐越亮太, 鵜飼 和代, 浪越 通夫
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] インドネシア産海洋糸状菌Penicillium verruculosum TPU1311株が生産する新規protein tyrosine phosphatase 1B阻害剤verruculide類に関する研究 (2016)
  • Author(s): 山崎寛之, 高橋央宜, 桐越亮太, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, 鵜飼和代, 浪越通夫
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] A new polyacetylene derivative with protein tyrosine phosphatase 1B inhibitory activity from the marine sponge Halicondria cf. panicea collected at Iriomote Island (2016)
  • Author(s): Delfly B. Abdjul, Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Kazuyo Ukai, and Michio Namikoshi
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] Structures and biological activities of new terpene metabolites obtained from the fruiting bodies of Russula lepida. (2016)
  • Author(s): Jong-Soo Lee, Wilmar Maarisit, Delfly B. Abdjul, Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Syu-ichi Kanno, and Michio Namikoshi
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] 天然由来化合物ライブラリーを基盤とした抗結核剤の探索 (2016)
  • Author(s): 中原悠太, 田中有理沙, 郡司雅奈子, Delfly B. Abdjul, 山崎寛之, 小山信裕, 浪越通夫, 供田 洋
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2016-03-28
• [Presentation] Marine natural products with protein tyrosine phosphatase 1B inhibitory activity (2015)
  • Author(s): Hiroyuki Yamazaki, Syu-ichi Kanno, Ohgi Takahashi, Ryota Kirikoshi, Delfly B. Abdjul, Kazuyo Ukai, Henki Rotinsulu, Defny S. Wewengkang, Deiske, A. Sumilat, Remy E. P. Mangindaan, Michio Namikoshi
  • Organizer: The International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] Induced production of new epidithiodiketopiperazines by the Palauan marine-derived fungus Trichoderma sp. TPU199 (2015)
  • Author(s): Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Michio Namikoshi
  • Organizer: The International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] 有用天然成分の探索と有効利用 (2015)
  • Author(s): 山崎 寛之, 鵜飼 和代, 浪越 通夫
  • Organizer: 産学官連携フェア2015みやぎ
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2015-12-09
• [Presentation] 海洋生物資源を対象としたprotein tyrosine phosphatase 1B阻害剤の探索と培養法検討による新規糸状菌二次代謝産物の誘導生産 (2015)
  • Author(s): 山崎 寛之, 浪越 通夫
  • Organizer: 第6回 食品薬学シンポジウム
  • Place of Presentation: 岡山大学 (岡山県岡山市)
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] インドネシア産放線菌が生産する二次代謝産物に関する研究 (2015)
  • Author(s): 山崎 寛之, 遠藤 幸太郎, 小笠原 彰希, 高橋 萌, 渡辺 祐太, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, 鵜飼 和代, 浪越 通夫
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学 (岩手県矢巾町)
  • Year and Date: 2015-09-26
• [Presentation] Polycyclic alkaloids from the marine sponge Halichondria panicea collected at Iriomote Island (2015)
  • Author(s): Delfly B. Abdjul, Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Kazuyo Ukai, Michio Namikoshi
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学 (岩手県矢巾町)
  • Year and Date: 2015-09-26
• [Presentation] Isolation and structure of a new chemical constituent from an Indonesian medicinal plant Rhinacanthus nasutus (2015)
  • Author(s): Wilmar Maarisit, Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Michio Namikoshi
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学 (岩手県矢巾町)
  • Year and Date: 2015-09-26
• [Presentation] 西表島産海綿 Halichondria panicea より得られた新規 halichondriamines の構造と生物活性 (2015)
  • Author(s): Delfly B. Abdjul, 山崎 寛之, 菅野 秀一, 高橋 央宜, 桐越 亮太, 鵜飼 和代, 浪越 通夫
  • Organizer: 第57回天然有機化合物討論会
  • Place of Presentation: 神奈川県民ホール (神奈川県横浜市)
  • Year and Date: 2015-09-09
• [Presentation] 海洋糸状菌Trichoderma sp. TPU1237株が生産する新規PTP1B 阻害物質に関する研究 (2015)
  • Author(s): 山﨑寛之, 斉藤 亮，高橋央宜, 桐越亮太, 虎岩憲吾, 岩﨑康平, 中山 渉, 泉川裕太, 浪越通夫
  • Organizer: 日本薬学会第135回年会
  • Place of Presentation: デザインクリエイティブセンター神戸(兵庫県神戸市)
  • Year and Date: 2015-03-27
• [Presentation] 西表島産海綿より見出した新規agelasine類の構造と抗結核活性 (2015)
  • Author(s): Delfly B. Abdjula, 山崎寛之, 高橋央宜, 桐越亮太, 浪越通夫
  • Organizer: 日本薬学会第135回年会
  • Place of Presentation: デザインクリエイティブセンター神戸(兵庫県神戸市)
  • Year and Date: 2015-03-27
• [Presentation] インドネシア産薬用植物Rhinacanthus nasutusの化学成分の単離と生物活性 (2015)
  • Author(s): Wilmar Maarisit, 山崎寛之, Delfly B. Abdjul, 浪越通夫
  • Organizer: 日本薬学会第135回年会
  • Place of Presentation: デザインクリエイティブセンター神戸(兵庫県神戸市)
  • Year and Date: 2015-03-27
• [Presentation] インドネシア産海洋生物資源から単離した新規PTP1B 阻害物質の構造と生物活性 (2014)
  • Author(s): Delfly B. Abdjula, 山﨑寛之, 高橋央宜, 桐越亮太, Remy E. P. Mangindaana, 浪越通夫
  • Organizer: 第56回天然有機化合物討論会
  • Place of Presentation: 三翠園(高知県高知市)
  • Year and Date: 2014-10-15
• [Presentation] 海洋糸状菌によるクルクミンの微生物変換 (2014)
  • Author(s): 山﨑寛之, 今野翔太, 岩﨑康平, 中山 渉, 泉川裕太, 虎岩憲吾, 浪越 通夫
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学(福島県いわき市)
  • Year and Date: 2014-10-05
• [Presentation] 西表島産海洋放線菌が生産する新規抗結核物質の構造と生物活性 (2014)
  • Author(s): 卜 英悦, 山﨑寛之, 鵜飼和代, 浪越通夫
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学(福島県いわき市)
  • Year and Date: 2014-10-05
• [Presentation] Isolation and structures of new indole derivatives from a marine sponge collected at Iriomote island. (2014)
  • Author(s): Delfly B. Abdjul, Hiroyuki Yamazaki, Kazuyo Ukai, and MichioNamikoshi
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学(福島県いわき市)
  • Year and Date: 2014-10-05
• [Presentation] パラオ産海洋糸状菌Trichoderma sp.TPU199株のDMSO添加培養による 新規epitrithiodiketopiperazineの生産誘導
  • Author(s): 山﨑寛之、村上一輝、藤原大夢、金子 剛、浪越通夫
  • Organizer: 第８回化学生態学研究会
  • Place of Presentation: 函館
• [Presentation] パラオ産海洋糸状菌Trichoderma sp. TPU199株による 新規epidithiodiketopiperazine類の生産誘導
  • Author(s): 山﨑寛之、Henki Rotinsulu、高橋央宜、浪越通夫
  • Organizer: 第５５回天然有機化合物討論会
  • Place of Presentation: 京都
• [Presentation] インドネシア産海洋糸状菌 Aspergillus sp. TPU011株の海水培地に よる物質生産の検討
  • Author(s): 千田一慶、山﨑寛之、Remy E. P. Mangindaan、浪越通夫
  • Organizer: 第５２回日本薬学会東北支部大会
  • Place of Presentation: 仙台
• [Presentation] パラオ産海洋糸状菌Trichoderma sp. から単離した epipolythiodiketopiperazine類の抗結核活性
  • Author(s): 山﨑寛之、成田麗加、高橋亮介、斉藤 亮、今野翔太、高橋央宜、浪越通夫
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本
• [Presentation] 青森県で採集した水圏由来糸状菌からの protein tyrosine phosphotase 1B 阻害剤の探索
  • Author(s): 山﨑寛之、斉藤 亮、菅野秀一、今野翔太、成田 麗加、高橋 亮介、石川正明、浪越通夫
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本
• [Remarks] 東北医科薬科大学 天然物化学教室
  • URL: http://www.tohoku-mpu.ac.jp/laboratory/tennen/site/index.html