A new linear type-1 polyketide, ionostatin (1), has been fully defined using a combined genomic and bioinformatics approach coupled with confirmatory chemical analyses. The 41 carbon-containing polyether is the product of the 101 kbp ion biosynthetic cluster containing seven modular type-1 polyketide synthases. Ionostatin is composed of 15 chiral centers that were proposed using the stereospecificities installed by the different classes of ketoreductases and enoylreductases and confirmed by rigorous NMR analyses. Incorporated into the structure are two tetrahydrofuran rings that appear to be the product of stereospecific epoxidation, followed by stereospecific ring opening and cyclization. These transformations are proposed to be catalyzed by conserved enzymes analogous to those found in other bacterial-derived polyether biosynthetic clusters. Ionostatin shows moderate cancer cell cytotoxicity against U87 glioblastoma and SKOV3 ovarian carcinoma at 7.4 μg/mL.

中文翻译：

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互补的基因组，生物信息学和化学方法可促进Ionostatin的绝对结构分配，Ionostatin是一种来自稀有海洋衍生的放线菌的线性聚酮化合物。

使用基因组学和生物信息学相结合的方法以及确定性的化学分析方法，已经完全定义了一种新的线性1型聚酮化合物ionostatin（1）。41个含碳聚醚是101 kbp离子的产物生物合成集群包含七个模块化的1型聚酮化合物合酶。离子抑制素由15个手性中心组成，这些中心是使用不同类别的酮还原酶和烯酰还原酶确定的立体特异性提出的，并通过严格的NMR分析加以证实。结合到结构中的是两个四氢呋喃环，它们似乎是立体有择的环氧化产物，随后是立体有择的开环和环化产物。提出这些转化是由保守酶催化的，该酶类似于在其他细菌衍生的聚醚生物合成簇中发现的那些酶。离子抑制素对7.4μg/ mL的U87胶质母细胞瘤和SKOV3卵巢癌显示出中等程度的癌细胞毒性。