CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, Institutions of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
Mar Drugs. 2019 Mar 4;17(3):150. doi: 10.3390/md17030150.
Diazobenzofluorene-containing atypical angucyclines exhibit promising biological activities. Here we report the inactivation of an amidotransferase-encoding gene in SCSIO N160, a producer of fluostatins. Bioinformatics analysis indicated that FlsN3 was involved in the diazo formation. Chemical investigation of the -inactivation mutant resulted in the isolation of a variety of angucycline aromatic polyketides, including four racemic aminobenzo[]fluorenes stealthins D⁻G (⁻) harboring a stealthin C-like core skeleton with an acetone or butanone-like side chain. Their structures were elucidated on the basis of nuclear magnetic resonance (NMR) spectroscopic data and X-ray diffraction analysis. A plausible mechanism for the formation of stealthins D⁻G (⁻) was proposed. These results suggested a functional role of FlsN3 in the formation/modification of N⁻N bond-containing fluostatins.
含重氮苯并菲的非典型蒽环类抗生素表现出有前景的生物活性。在这里，我们报道了杀假丝菌素 N160 中一种酰胺转移酶编码基因的失活，该菌是杀假丝菌素的产生菌。生物信息学分析表明 FlsN3 参与了重氮的形成。对失活突变体的化学研究导致了多种蒽环类芳香聚酮的分离，包括四种含有 stealthin C 样核心骨架和丙酮或丁酮样侧链的对映体氨基苯并[]荧光酮 stealthins D⁻G (⁻)。它们的结构是基于核磁共振（NMR）波谱数据和 X 射线衍射分析确定的。提出了 stealthins D⁻G (⁻) 形成的合理机制。这些结果表明 FlsN3 在含 N⁻N 键的杀假丝菌素的形成/修饰中具有功能作用。
