Abstract
β-Carboline alkaloids and related compounds show a broad spectrum of biological activities. We previously identified new members of the β-carboline alkaloid family by using an engineered Kitasatospora setae strain and a heterologous Streptomyces host expressing the plausible biosynthetic genes, including the hypothetical gene kse_70640 (kslB). Here, we elucidated the chemical structure of a new tetrahydro-β-carboline compound (named kitasetalic acid) that appeared in a heterologous Streptomyces host expressing the kslB gene alone. Kitasetalic acid suppressed the expression of glucose-regulated protein 78 (GRP78) without inducing cell death. This is the first report to show that a tetrahydro-β-carboline compound regulates the expression of the GRP78 protein in cancer cell lines.
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research (C) (Grant Number JP15K07358) from the Japan Society for the Promotion of Science to S.K. and by a New Chemical Technology Research Encouragement Award from the Japan Association for Chemical Innovation to S.K.
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Ueda, S., Kitani, S., Namba, T. et al. Engineered production of kitasetalic acid, a new tetrahydro-β-carboline with the ability to suppress glucose-regulated protein synthesis. J Antibiot 71, 854–861 (2018). https://doi.org/10.1038/s41429-018-0074-7
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DOI: https://doi.org/10.1038/s41429-018-0074-7
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