Search for Protein Tyrosine Phosphatase 1B Inhibitors from Marine Organisms and Induced Production of New Fungal Metabolites by Modulating Culture Methods

Yamazaki Hiroyuki

doi:10.1248/yakushi.18-00221

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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 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

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Abstract

<p>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.</p>

Journal

YAKUGAKU ZASSHI

YAKUGAKU ZASSHI 139 (5), 663-672, 2019-05-01

The Pharmaceutical Society of Japan

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