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.

中文翻译：

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工程化生产Kitasetalic acid，一种新型的四氢-β-咔啉，具有抑制葡萄糖调节的蛋白质合成的能力。

β-Carboline生物碱和相关化合物具有广泛的生物活性。我们之前使用工程化的Kitasatospora setae菌株和表达合理生物合成基因（包括假设基因kse_70640（kslB））的异源链霉菌宿主，鉴定了β-咔啉生物碱家族的新成员。在这里，我们阐明了出现在仅表达kslB基因的异源链霉菌宿主中的一种新的四氢-β-咔啉化合物（称为Kitasetalic酸）的化学结构。Kitasetalic acid抑制葡萄糖调节蛋白78（GRP78）的表达，而不会引起细胞死亡。这是第一个显示四氢-β-咔啉化合物调节癌细胞系中GRP78蛋白表达的报道。