Trierixin, a novel inhibitor of ER stress-induced XBP1 activation from Streptomyces sp. I. Taxonomy, fermentation, isolation, and biological activities

Etsu Tashiro, Naoka Hironiwa, Mitsuhiro Kitagawa, Yushi Futamura, Shin Ichi Suzuki, Maki Nishio, Masaya Imoto

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In the course of screening for an inhibitor of ER stress-induced XBP1 activation, we isolated a new member of the triene-ansamycin group compound, trierixin, from a culture broth of Streptomyces sp. AC 654. Trierixin was purified by column chromatography on silica gel and by HPLC. The molecular formula of trierixin is C37H52N2O8S. Trierixin inhibited thapsigargin-induced XBP1-luciferase activation in HeLa/XBP1-luc cells and endogenous XBP1 splicing in HeLa cells with an IC 50 of 14 ng/ml and 19 ng/ml, respectively. Moreover, in the process of isolating trierixin, we isolated structurally related mycotrienin II and trienomycin A as inhibitors of ER stress-induced XBP1 activation from a culture broth of a trierixin-producing strain. This study provides the first observation that triene-ansamycins have a novel inhibitory effect against XBP1 activation.

Original languageEnglish
Pages (from-to)547-553
Number of pages7
JournalJournal of Antibiotics
Volume60
Issue number9
DOIs
Publication statusPublished - 2007 Sep 1

Keywords

  • ER stress
  • Triene-ansamycin
  • Trierixin
  • XBP1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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