Discovery of a New Natural Product from Marine-Derived Micromonospora Guided by the Biosynthetic Studies of Kosinostatin

Kosinostatin (KST), isolated from the fermentation extraction of Micromonospora sp. TP-A0468, is a kind of anthraquinones antibiotic with antitumor activity. To investigate the function of kstD3 gene, encoding a sugar 3,5-epimerase involved in the KST biosynthetic gene cluster, the gene disruption mutant strain Micromonospora sp. TP-A0468 mKOSD3 is constructed. A novel compound, deoxy-isoquinocycline B was discovered and isolated from this mutant strain and its structure was characterized by comparison to the HRMS and NMR spectra of isoquinocycline B. This compound could be considered as an analogue of isoquinocycline B. Compared with isoquinocycline B, its antitumor activity decreased significantly. It is also found that the glycosyltransferase KstD5 is more substrate-flexible than anticipated, which lay the foundation for further using the characteristics of this enzyme to obtain more analogues.