海洋生物由来protein tyrosine phosphatase 1B阻害剤に関する研究及び培養法検討による新規糸状菌二次代謝産物の誘導生産

• 山﨑 寛之

  東北医科薬科大学薬学部天然物化学教室

書誌事項

タイトル別名

• Search for Protein Tyrosine Phosphatase 1B Inhibitors from Marine Organisms and Induced Production of New Fungal Metabolites by Modulating Culture Methods
• Review for award 海洋生物由来protein tyrosine phosphatase 1B阻害剤に関する研究及び培養法検討による新規糸状菌二次代謝産物の誘導生産
• Review for award カイヨウ セイブツ ユライ protein tyrosine phosphatase 1B ソガイザイ ニ カンスル ケンキュウ オヨビ バイヨウホウ ケントウ ニ ヨル シンキ シジョウキン ニジ タイシャ サンブツ ノ ユウドウ セイサン

抄録

Marine environments offer a rich source of natural products with potential therapeutic applications because the ocean covers 70% of the earth's surface and approximately 80% of all living organisms live in the sea. Therefore we have investigated bioactive compounds from marine organisms such as marine sponges, ascidians, and marine-derived microorganisms. This review consists of two topics based on marine natural product chemistry. (1) Protein tyrosine phosphatase (PTP) 1B plays a key role as a negative regulator in the insulin and leptin signaling pathways. Accordingly, the development of PTP1B inhibitors is expected to provide new drugs for type 2 diabetes and obesity. We have been searching for new types of PTP1B inhibitors among marine organisms and identified various PTP1B inhibitors from marine sponges and fungi. This review presents their structural diversities and unique biological properties. (2) In the course of our studies on the induced production of new fungal metabolites, the Palauan marine-derived fungus, Trichoderma cf. brevicompactum TPU199, was found to produce the unusual epipolythiodiketopiperazines, gliovirin and pretrichodermamide A. Long-term static fermentation of the strain induced production of a new dipeptide, dithioaspergillazine A, whereas fermentation of the strain with NaCl, NaBr, and NaI produced the Cl and Br derivatives of pretrichodermamide A and a new iodinated derivative, iododithiobrevamide, respectively. Moreover, DMSO-added seawater medium induced the production of diketopiperazine with the unprecedented trithio-bridge, chlorotrithiobrevamide. This fermentation study on the strain as well as the structures of the metabolites obtained are described in this review.

収録刊行物

• 薬学雑誌

  薬学雑誌 139 (5), 663-672, 2019-05-01

  公益社団法人 日本薬学会

キーワード

• marine organism
• protein tyrosine phosphatase 1B
• induced production
• microbial secondary metabolite
• epipolythiodiketopiperazine

詳細情報

• CRID: 1390564238088335104
• NII論文ID: 130007641022
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.18-00221
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 029709448
• PubMed: 31061333
• Web Site: http://id.ndl.go.jp/bib/029709448
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029709448
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/139/5/139_18-00221/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020003578
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可