期刊
MARINE DRUGS
卷 17, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/md17030150
关键词
angucyclines; N-N bond; raceme; gene inactivation; biosynthesis; marine; Micromonospora
资金
- National Natural Science Foundation of China [31820103003, 31700042, 41676165]
- Guangdong Province [GDME-2018C005, 2015A030308013]
- Chinese Academy of Sciences [QYZDJ-SSW-DQC004]
Diazobenzofluorene-containing atypical angucyclines exhibit promising biological activities. Here we report the inactivation of an amidotransferase-encoding gene flsN3 in Micromonospora rosaria SCSIO N160, a producer of fluostatins. Bioinformatics analysis indicated that FlsN3 was involved in the diazo formation. Chemical investigation of the flsN3-inactivation mutant resulted in the isolation of a variety of angucycline aromatic polyketides, including four racemic aminobenzo[b]fluorenes stealthins D-G (9-12) 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 (9-12) was proposed. These results suggested a functional role of FlsN3 in the formation/modification of N-N bond-containing fluostatins.
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