title: Trierixin, a novel Inhibitor of ER stress-induced XBP1 activation from Streptomyces sp. 1. Taxonomy, fermentation, isolation and biological activities.
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 C(37)H(52)N(2)O(8)S. 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.
authors.affiliation: Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan. tashiro@bio.keio.ac.jp
authors.forename: Etsu
authors.initials: E
authors.lastname: Tashiro
authors.forename: Naoka
authors.initials: N
authors.lastname: Hironiwa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Yushi
authors.initials: Y
authors.lastname: Futamura
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Maki
authors.initials: M
authors.lastname: Nishio
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000145:classification / Q000302:isolation & purification / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005285:Fermentation; D006367:HeLa Cells; D006801:Humans; D006873:Hydroquinones / Q000302:isolation & purification; D020128:Inhibitory Concentration 50; D047029:Lactams, Macrocyclic / Q000145:classification / Q000302:isolation & purification / Q000494:pharmacology*; D008156:Luciferases / Q000187:drug effects; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013302:Streptomyces / Q000737:chemistry*; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology; D019284:Thapsigargin; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
chemical_list: D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D006873:Hydroquinones; D047029:Lactams, Macrocyclic; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C525271:trierixin; D019284:Thapsigargin; C036971:mycotrienin II; C045958:trienomycin A; D008156:Luciferases; D000409:Alanine