Engineered production of kitasetalic acid, a new tetrahydro-β-carboline with the ability to suppress glucose-regulated protein synthesis

Abstract

© 2018, The Author(s) under exclusive licence to the Japan Antibiotics Research Association. 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.