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 IC50 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.
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Tashiro, E., Hironiwa, N., Kitagawa, M. et al. Trierixin, a Novel Inhibitor of ER Stress-induced XBP1 Activation from Streptomyces sp.. J Antibiot 60, 547–553 (2007). https://doi.org/10.1038/ja.2007.69
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DOI: https://doi.org/10.1038/ja.2007.69
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