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

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 nogalamycinbiosynthesis and its modification by way of combinatorial biosynthesis.biosynthesis and its modification by way of combinatorial biosynthesis.