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该基因对于诺加霉素生物合成途径的正常运作是必需的。

The Gene is Necessary for the Proper Functioning of the Nogalamycin Biosynthesis Pathway.

作者信息

Li Mengxi, Zhang Zhenwang

机构信息

College of Clinical Medicine, HuBei University of Science and Technology, Xianning, China.

College of Chemical and Biological Engineering, Hechi University, Yizhou, 546300 Guangxi China.

出版信息

Indian J Microbiol. 2021 Dec;61(4):467-474. doi: 10.1007/s12088-021-00941-7. Epub 2021 May 7.

Abstract

Anthracycline drugs have multifunctional molecular structures, and small changes in the structure of the glycosyls around the chromophore affect their mechanism of action, pharmacokinetics, toxicity, anti-tumor activity, and many other significant parameters.  has a similar function to but inverse stereoselectivity. encoding amino transferase was substituted for for the purpose of obtaining nogalamycin analogues. We inactivated the gene encoding an aminotransferase responsible for the formation of nogalamine and introduced the gene encoding an aminotransferase responsible for the formation of daunosamine. We obtained the recombinant strain mLMX-3-100, in which the production of nogalamycin was disrupted. Interestingly, contrary to our predictions, no epi-nogalamycin was produced; nevertheless, the present study shows that the gene is necessary for the proper functioning of the nogalamycin biosynthesis pathway. These data may provide a reference for further illustration of nogalamycin biosynthesis and its modification by way of combinatorial biosynthesis.biosynthesis and its modification by way of combinatorial biosynthesis.

摘要

蒽环类药物具有多功能分子结构,发色团周围糖基结构的微小变化会影响其作用机制、药代动力学、毒性、抗肿瘤活性以及许多其他重要参数。 与 具有相似功能,但立体选择性相反。为了获得诺加霉素类似物,将编码氨基转移酶的 替换为 。我们使负责去甲万古胺形成的氨基转移酶编码基因 失活,并引入负责柔红糖胺形成的氨基转移酶编码基因 。我们获得了重组菌株mLMX - 3 - 100,其中诺加霉素的产生被破坏。有趣的是,与我们的预测相反,没有产生表诺加霉素;然而,本研究表明 基因对于诺加霉素生物合成途径的正常运作是必需的。这些数据可为进一步阐明诺加霉素生物合成及其通过组合生物合成进行修饰提供参考。通过组合生物合成进行生物合成及其修饰。

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Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R.酶法合成诺加霉素 R 的 C-糖苷部分。
ACS Chem Biol. 2018 Sep 21;13(9):2433-2437. doi: 10.1021/acschembio.8b00658. Epub 2018 Aug 20.

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Anthracyclines as effective anticancer drugs.蒽环类药物作为有效的抗癌药物。
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