%0 Journal Article
%T Discovery of Stealthin Derivatives and Implication of the Amidotransferase FlsN3 in the Biosynthesis of Nitrogen-Containing Fluostatins.
%A Huang C
%A Yang C
%A Fang Z
%A Zhang L
%A Zhang W
%A Zhu Y
%A Zhang C
%J Mar Drugs
%V 17
%N 3
%D Mar 2019 4
%M 30836614
%F 6.085
%R 10.3390/md17030150
%X 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.