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. DnrJ has a similar function to snogI but inverse stereoselectivity. SnogI encoding amino transferase was substituted for DnrJ for the purpose of obtaining nogalamycin analogues. We inactivated the snogI gene encoding an aminotransferase responsible for the formation of nogalamine and introduced the dnrJ 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 snogI 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.

中文翻译：

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snogI 基因对于诺加霉素生物合成途径的正常运作是必需的

摘要

蒽环类药物具有多功能的分子结构，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、抗肿瘤活性和许多其他重要参数。 DnrJ具有与snogI类似的功能，但具有逆立体选择性。为了获得诺加霉素类似物，将编码氨基转移酶的SnogI替换为DnrJ 。我们灭活了编码负责形成nogalamine的转氨酶的snogI基因，并引入了编码负责形成道诺糖胺的转氨酶的dnrJ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，没有产生表加霉素；然而，本研究表明snogI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的生物合成及其组合生物合成修饰提供参考。生物合成及其组合生物合成修饰。