Recently described rhizolutin and collinolactone isolated from Streptomyces Gö 40/10 share the same novel carbon scaffold. Analyses by NMR and X-Ray crystallography verify the structure of collinolactone and propose a revision of rhizolutin's stereochemistry. Isotope-labeled precursor feeding shows that collinolactone is biosynthesized via type I polyketide synthase with Baeyer–Villiger oxidation. CRISPR-based genetic strategies led to the identification of the biosynthetic gene cluster and a high-production strain. Chemical semisyntheses yielded collinolactone analogues with inhibitory effects on L929 cell line. Fluorescence microscopy revealed that only particular analogues induce monopolar spindles impairing cell division in mitosis. Inspired by the Alzheimer-protective activity of rhizolutin, we investigated the neuroprotective effects of collinolactone and its analogues on glutamate-sensitive cells (HT22) and indeed, natural collinolactone displays distinct neuroprotection from intracellular oxidative stress.

中文翻译：

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环癸三烯可利诺内酯的结构、生物合成和半合成类似物：单星形表型的影响和细胞内氧化应激的保护

最近描述的从 Streptomyces Gö 40/10 中分离出的根瘤菌素和可利诺内酯共享相同的新型碳支架。核磁共振和 X 射线晶体学分析证实了可利诺内酯的结构，并提出了对根霉的立体化学的修正。同位素标记的前体补料表明，可利内酯是通过 I 型聚酮合酶和 Baeyer-Villiger 氧化进行生物合成的。基于 CRISPR 的遗传策略导致了生物合成基因簇和高产菌株的鉴定。化学半合成产生了对 L929 细胞系具有抑制作用的可林内酯类似物。荧光显微镜显示只有特定的类似物才能诱导单极纺锤体，从而损害有丝分裂中的细胞分裂。受根霉酚的阿尔茨海默保护活性的启发，